包含IL-2蛋白和CD80蛋白片段或其变体的融合蛋白及其用途
文献发布时间：2023-06-19 19:28:50
技术领域
本发明涉及包含IL-2蛋白和CD80蛋白片段或其变体的融合蛋白及其用途。具体而言，本发明涉及具有免疫增强功效的用于治疗癌症的新型融合蛋白。
背景技术
白细胞介素2(IL-2)，也称为T细胞生长因子(TCGF)，是一种在淋巴细胞的产生、存活和稳态中起核心作用的球状糖蛋白。IL-2的蛋白质大小为15.5kDa至16kDa，由133个氨基酸组成。IL-2通过与由三个不同亚基组成的IL-2受体结合来介导各种免疫作用。
此外，IL-2主要由活化的T细胞合成，特别是由CD4+辅助T细胞合成。IL-2刺激T细胞的增殖和分化，并诱导细胞毒性T淋巴细胞(CTL)的产生和外周血淋巴细胞分化为细胞毒性细胞和淋巴因子活化的杀伤细胞(LAK细胞)。
此外，IL-2参与B细胞的增殖和分化，促进B细胞合成免疫球蛋白，并刺激自然杀伤细胞(NK细胞)的产生、增殖和活化。因此，IL-2被用作抗癌剂，因为它可以增加淋巴细胞数量并增强活体内免疫细胞的功能。目前，用IL-2进行治疗已获批准并用于转移性肾细胞癌和恶性黑色素瘤患者。
然而，IL-2在免疫反应中具有双重功能，因为它不仅对介导增加免疫细胞数量及增强其活性很重要，而且对维持免疫耐受也很重要。此外，据报道，IL-2可能不是抑制肿瘤生长的最佳选择。原因是在IL-2存在的情况下，活化诱导的细胞死亡(AICD)可能发生在所产生的细胞毒性T淋巴细胞中，并且免疫反应可能被IL-2依赖性调节性T细胞(Treg细胞)抑制(Imai et al.,Cancer Sci 98,416-423,2007)。
此外，接受IL-2免疫治疗的患者会出现严重的心血管、肺部、肾脏、肝脏、胃肠道、神经元、皮肤、血液和全身性副作用。因此，已经研究了多种IL-2突变体以提高IL-2的治疗作用并使其副作用最小化(US5,229,109B)。然而，为了将IL-2用于药理学目的，仍有许多问题需要解决。
另一方面，CD80，也称为B7-1，是膜结合蛋白B7家族的成员，该B7家族通过与其配体结合，凭借传递共刺激反应和共抑制反应来参与免疫调节。CD80是一种表达于T细胞、B细胞、树突细胞和单核细胞表面上的跨膜蛋白。已知CD80与CD28、CTLA4(CD152)和PD-L1结合。CD80、CD86、CTLA4和CD28参与共刺激-共抑制系统。例如，它们调节T细胞的活性并参与T细胞的增殖、分化和存活。
例如，当CD80和CD86与CD28相互作用时，会产生共刺激信号以活化T细胞。最终，CD80与在活化的T细胞的表面上表达的CTLA4结合，并刺激CTLA4上调。因此，CD80在由CD80/CD28相互作用引起的免疫反应操作之前抑制T细胞反应。该反馈回路允许对免疫反应进行精细调节。
此外，已知CD80与另一个B7家族成员PD-L1结合，其亲和力类似于CD28与PD-L1结合的亲和力。PD-L1被称为程序性死亡-1(PD-1)蛋白的两种配体之一，并且已知PD-L1参与T细胞调节。CD80与PD-L1的结合是另一种可以阻断PD-1/PD-L1相互作用的机制，这可能会阻止对肿瘤中对T细胞反应的抑制。然而，与此同时，CD80水平的升高会导致CD80与CD28结合，以便诱导CTLA4，从而诱导或抑制T细胞反应。
发明内容
技术问题
本发明人进行了研究以开发安全有效的IL-2。结果，本发明人发现在一个分子中包含IL-2蛋白和CD80蛋白片段或其变体的新型融合蛋白可以活化免疫细胞并有效调节Treg细胞，从而完成了本发明。
解决方案
为了实现上述目的，在本发明的一个方面，提供了一种融合蛋白，其包含IL-2蛋白和CD80蛋白片段或其变体。
在本发明的另一个方面，提供了通过将两个该融合蛋白彼此结合而获得的融合蛋白二聚体。
在本发明的又一方面，提供了编码该融合蛋白的多核苷酸。
在本发明的又一方面，提供了包含该多核苷酸的运载体。
在本发明的又一方面，提供了已导入该运载体的转化细胞。
在本发明的又一方面，提供了用于预防或治疗癌症或传染病的药物组合物，该药物组合物包含该融合蛋白或该融合蛋白二聚体作为活性成分。
在本发明的又一方面，提供了该融合蛋白用于治疗癌症或传染病的用途。
在本发明的再一方面，提供了该融合蛋白在制备用于治疗癌症或传染病的药物中的用途。
发明效果
包含IL-2蛋白和CD80蛋白片段或其变体的融合蛋白不仅可以通过IL-2活化免疫细胞，还可以通过CD80有效调节Treg细胞。因此，该融合蛋白可以有效地攻击癌细胞，并因此可以有效地用于治疗癌症或传染病。
附图说明
图1示出了GI-101_P1的组成部分及其肽序列(CD80：SEQ ID NO:38，接头1：SEQ IDNO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P1：SEQ ID NO:39)。
图2示出了GI-101_P2的组成部分及其肽序列(CD80：SEQ ID NO:40，接头1：SEQ IDNO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P2：SEQ ID NO:41)。
图3示出了GI-101_P3的组成部分及其肽序列(CD80：SEQ ID NO:42，接头1：SEQ IDNO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P3：SEQ ID NO:43)。
图4示出了GI-101_P4的组成部分及其肽序列(CD80：SEQ ID NO:44，接头1：SEQ IDNO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P4：SEQ ID NO:45)。
图5示出了GI-101_P5的组成部分及其肽序列(CD80：SEQ ID NO:46，接头1：SEQ IDNO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P5：SEQ ID NO:47)。
图6示出了GI-101_P6的组成部分及其肽序列(CD80：SEQ ID NO:48，接头1：SEQ IDNO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P6：SEQ ID NO:49)。
图7示出了GI-101_P7的组成部分及其肽序列(CD80：SEQ ID NO:50，接头1：SEQ IDNO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P7：SEQ ID NO:51)。
图8示出了GI-101_P8的组成部分及其肽序列(CD80：SEQ ID NO:52，接头1：SEQ IDNO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P8：SEQ ID NO:53)。
图9示出了GI-101_P9的组成部分及其肽序列(CD80：SEQ ID NO:54，接头1：SEQ IDNO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P9：SEQ ID NO:55)。
图10示出了GI-101_P10的组成部分及其肽序列(CD80：SEQ ID NO:56，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P10：SEQ IDNO:57)。
图11示出了GI-101_P11的组成部分及其肽序列(CD80：SEQ ID NO:58，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P11：SEQ IDNO:59)。
图12示出了GI-101_P12的组成部分及其肽序列(CD80：SEQ ID NO:60，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P12：SEQ IDNO:61)。
图13示出了GI-101_P13的组成部分及其肽序列(CD80：SEQ ID NO:62，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P13：SEQ IDNO:63)。
图14示出了GI-101_P14的组成部分及其肽序列(CD80：SEQ ID NO:64，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P14：SEQ IDNO:65)。
图15示出了GI-101_P15的组成部分及其肽序列(CD80：SEQ ID NO:66，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P15：SEQ IDNO:67)。
图16示出了GI-101_P16的组成部分及其肽序列(CD80：SEQ ID NO:68，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P16：SEQ IDNO:69)。
图17示出了GI-101_P17的组成部分及其肽序列(CD80：SEQ ID NO:70，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P17：SEQ IDNO:71)。
图18示出了GI-101_P18的组成部分及其肽序列(CD80：SEQ ID NO:72，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P18：SEQ IDNO:73)。
图19示出了GI-101_P19的组成部分及其肽序列(CD80：SEQ ID NO:74，接头1：SEQID NO:3，Fc：SEQ ID NO:4，IL2V：SEQ ID NO:6，GI101_P19：SEQ ID NO:75)。
图20示出了GI-101_P20的组成部分及其肽序列(CD80：SEQ ID NO:74，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:76，IL2V：SEQ ID NO:6，GI101_P20：SEQ IDNO:77)。
图21示出了GI-101_P21的组成部分及其肽序列(CD80：SEQ ID NO:74，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:78，IL2V：SEQ ID NO:6，GI101_P21：SEQ IDNO:79)。
图22示出了GI-101_P22的组成部分及其肽序列(CD80：SEQ ID NO:74，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:80，IL2V：SEQ ID NO:6，GI101_P22：SEQ IDNO:81)。
图23示出了GI-101_P23的组成部分及其肽序列(CD80：SEQ ID NO:74，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:82，IL2V：SEQ ID NO:6，GI101_P23：SEQ IDNO:83)。
图24示出了GI-101_P24的组成部分及其肽序列(CD80：SEQ ID NO:74，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:84，IL2V：SEQ ID NO:6，GI101_P24：SEQ IDNO:85)。
图25示出了GI-101_P25的组成部分及其肽序列(CD80：SEQ ID NO:74，接头1：SEQID NO:86，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P25：SEQ IDNO:87)。
图26示出了GI-101_P26的组成部分及其肽序列(CD80：SEQ ID NO:74，接头1：SEQID NO:88，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P26：SEQ IDNO:89)。
图27示出了GI-101_P27的组成部分及其肽序列(CD80：SEQ ID NO:74，接头1：SEQID NO:90，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P27：SEQ IDNO:91)。
图28示出了GI-101_P28的组成部分及其肽序列(CD80：SEQ ID NO:74，接头1：SEQID NO:92，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P28：SEQ IDNO:93)。
图29示出了GI-101_P29的组成部分及其肽序列(CD80：SEQ ID NO:74，接头1：SEQID NO:94，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P29：SEQ IDNO:95)。
图30示出了GI-101_P30的组成部分及其肽序列(CD80：SEQ ID NO:74，接头1：SEQID NO:96，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P30：SEQ IDNO:97)。
图31示出了GI-101_P31的组成部分及其肽序列(CD80：SEQ ID NO:74，接头1：SEQID NO:98，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6，GI101_P31：SEQ IDNO:99)。
图32示出了GI-101_P32的组成部分及其肽序列(CD80：SEQ ID NO:74，接头：SEQID NO:100，IL2V：SEQ ID NO:6，GI101_P32：SEQ ID NO:101)。
图33示出了GI-101_P33的组成部分及其肽序列(CD80：SEQ ID NO:74，接头：SEQID NO:102，IL2V：SEQ ID NO:6，GI101_P33：SEQ ID NO:103)。
图34示出了GI-101_P34的组成部分及其肽序列(CD80：SEQ ID NO:74，接头：SEQID NO:104，IL2V：SEQ ID NO:6，GI101_P34：SEQ ID NO:105)。
图35示出了GI-101_P35的组成部分及其肽序列(CD80：SEQ ID NO:74，接头：SEQID NO:106，IL2V：SEQ ID NO:6，GI101_P35：SEQ ID NO:107)。
图36示出了GI-101_P36至GI-101_P42，它们包含：CD80的变体和包含两个变异的IL-2的变体。
图37示出了GI-101_P36的组成部分及其肽序列(CD80：SEQ ID NO:108，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6)。
图38示出了GI-101_P37的组成部分及其肽序列(CD80：SEQ ID NO:109，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6)。
图39示出了GI-101_P38的组成部分及其肽序列(CD80：SEQ ID NO:110，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6)。
图40示出了GI-101_P39的组成部分及其肽序列(CD80：SEQ ID NO:111，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6)。
图41示出了GI-101_P40的组成部分及其肽序列(CD80：SEQ ID NO:112，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6)。
图42示出了GI-101_P41的组成部分及其肽序列(CD80：SEQ ID NO:113，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6)。
图43示出了GI-101_P42的组成部分及其肽序列(CD80：SEQ ID NO:114，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:6)。
图44示出了GI-101_P43至GI-101_P49，它们包含：CD80的变体和包含三个变异的IL-2的变体。
图45示出了GI-101_P43的组成部分及其肽序列(CD80：SEQ ID NO:108，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:115)。
图46示出了GI-101_P44的组成部分及其肽序列(CD80：SEQ ID NO:109，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:115)。
图47示出了GI-101_P45的组成部分及其肽序列(CD80：SEQ ID NO:110，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:115)。
图48示出了GI-101_P46的组成部分及其肽序列(CD80：SEQ ID NO:111，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:115)。
图49示出了GI-101_P47的组成部分及其肽序列(CD80：SEQ ID NO:112，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:115)。
图50示出了GI-101_P48的组成部分及其肽序列(CD80：SEQ ID NO:113，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:115)。
图51示出了GI-101_P49的组成部分及其肽序列(CD80：SEQ ID NO:114，接头1：SEQID NO:3，Fc：SEQ ID NO:4，接头2：SEQ ID NO:5，IL2V：SEQ ID NO:115)。
图52示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P1融合蛋白而获得的结果。
图53示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P2融合蛋白而获得的结果。
图54示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P3融合蛋白而获得的结果。
图55示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P4融合蛋白而获得的结果。
图56示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P5融合蛋白而获得的结果。
图57示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P6融合蛋白而获得的结果。
图58示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P7融合蛋白而获得的结果。
图59示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P8融合蛋白而获得的结果。
图60示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P9融合蛋白而获得的结果。
图61示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P10融合蛋白而获得的结果。
图62示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P11融合蛋白而获得的结果。
图63示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P12融合蛋白而获得的结果。
图64示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P13融合蛋白而获得的结果。
图65示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P14融合蛋白而获得的结果。
图66示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P15融合蛋白而获得的结果。
图67示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P16融合蛋白而获得的结果。
图68示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P17融合蛋白而获得的结果。
图69示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P18融合蛋白而获得的结果。
图70示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P19融合蛋白而获得的结果。
图71示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P20融合蛋白而获得的结果。
图72示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P21融合蛋白而获得的结果。
图73示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P22融合蛋白而获得的结果。
图74示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P23融合蛋白而获得的结果。
图75示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P24融合蛋白而获得的结果。
图76示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P25融合蛋白而获得的结果。
图77示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P26融合蛋白而获得的结果。
图78示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P27融合蛋白而获得的结果。
图79示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P28融合蛋白而获得的结果。
图80示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P29融合蛋白而获得的结果。
图81示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P30融合蛋白而获得的结果。
图82示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P31融合蛋白而获得的结果。
图83示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P32融合蛋白而获得的结果。
图84示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P33融合蛋白而获得的结果。
图85示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P34融合蛋白而获得的结果。
图86示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P35融合蛋白而获得的结果。
图87示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P1融合蛋白而获得的结果。
图88示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P2融合蛋白而获得的结果。
图89示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P3融合蛋白而获得的结果。
图90示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P4融合蛋白而获得的结果。
图91示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P5融合蛋白而获得的结果。
图92示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P6融合蛋白而获得的结果。
图93示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P7融合蛋白而获得的结果。
图94示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P8融合蛋白而获得的结果。
图95示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P9融合蛋白而获得的结果。
图96示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P10融合蛋白而获得的结果。
图97示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P11融合蛋白而获得的结果。
图98示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P12融合蛋白而获得的结果。
图99示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P13融合蛋白而获得的结果。
图100示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P14融合蛋白而获得的结果。
图101示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P15融合蛋白而获得的结果。
图102示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P16融合蛋白而获得的结果。
图103示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P17融合蛋白而获得的结果。
图104示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P18融合蛋白而获得的结果。
图105示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P19融合蛋白而获得的结果。
图106示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P20融合蛋白而获得的结果。
图107示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P21融合蛋白而获得的结果。
图108示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P22融合蛋白而获得的结果。
图109示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P23融合蛋白而获得的结果。
图110示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P24融合蛋白而获得的结果。
图111示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P25融合蛋白而获得的结果。
图112示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P26融合蛋白而获得的结果。
图113示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P27融合蛋白而获得的结果。
图114示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P28融合蛋白而获得的结果。
图115示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P29融合蛋白而获得的结果。
图116示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P30融合蛋白而获得的结果。
图117示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P31融合蛋白而获得的结果。
图118示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P32融合蛋白而获得的结果。
图119示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P33融合蛋白而获得的结果。
图120示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P34融合蛋白而获得的结果。
图121示出了通过尺寸排阻色谱法(SEC)分析根据本发明实施方式获得的GI-101_P35融合蛋白而获得的结果。
图122示出了根据本发明实施方式获得的GI-101_P1融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图123示出了根据本发明实施方式获得的GI-101_P2融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图124示出了根据本发明实施方式获得的GI-101_P3融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图125示出了根据本发明实施方式获得的GI-101_P4融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图126示出了根据本发明实施方式获得的GI-101_P5融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图127示出了根据本发明实施方式获得的GI-101_P6融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图128示出了根据本发明实施方式获得的GI-101_P7融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图129示出了根据本发明实施方式获得的GI-101_P8融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图130示出了根据本发明实施方式获得的GI-101_P9融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图131示出了根据本发明实施方式获得的GI-101_P10融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图132示出了根据本发明实施方式获得的GI-101_P11融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图133示出了根据本发明实施方式获得的GI-101_P12融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图134示出了根据本发明实施方式获得的GI-101_P13融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图135示出了根据本发明实施方式获得的GI-101_P14融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图136示出了根据本发明实施方式获得的GI-101_P15融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图137示出了根据本发明实施方式获得的GI-101_P16融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图138示出了根据本发明实施方式获得的GI-101_P17融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图139示出了根据本发明实施方式获得的GI-101_P18融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图140示出了根据本发明实施方式获得的GI-101_P19融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图141示出了根据本发明实施方式获得的GI-101_P20融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图142示出了根据本发明实施方式获得的GI-101_P21融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图143示出了根据本发明实施方式获得的GI-101_P22融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图144示出了根据本发明实施方式获得的GI-101_P23融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图145示出了根据本发明实施方式获得的GI-101_P24融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图146示出了根据本发明实施方式获得的GI-101_P25融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图147示出了根据本发明实施方式获得的GI-101_P26融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图148示出了根据本发明实施方式获得的GI-101_P27融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图149示出了根据本发明实施方式获得的GI-101_P28融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图150示出了根据本发明实施方式获得的GI-101_P29融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图151示出了根据本发明实施方式获得的GI-101_P30融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图152示出了根据本发明实施方式获得的GI-101_P31融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图153示出了根据本发明实施方式获得的GI-101_P32融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图154示出了根据本发明实施方式获得的GI-101_P33融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图155示出了根据本发明实施方式获得的GI-101_P34融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图156示出了根据本发明实施方式获得的GI-101_P35融合蛋白与CTLA-4或IL-2Rβ之间的结合亲和力。
图157示出了通过用SDS-PAGE鉴定根据本发明实施方式获得的GI-101_P36至GI-101_P49融合蛋白而获得的结果。
图158示出了根据本发明实施方式获得的GI-101_P36融合蛋白与IL-2Rβ、CTLA-4或PD-L1之间的结合亲和力。
图159示出了根据本发明实施方式获得的GI-101_P37融合蛋白与IL-2Rβ、CTLA-4或PD-L1之间的结合亲和力。
图160示出了根据本发明实施方式获得的GI-101_P38融合蛋白与IL-2Rβ、CTLA-4或PD-L1之间的结合亲和力。
图161示出了根据本发明实施方式获得的GI-101_P39融合蛋白与IL-2Rβ、CTLA-4或PD-L1之间的结合亲和力。
图162示出了根据本发明实施方式获得的GI-101_P40融合蛋白与IL-2Rβ、CTLA-4或PD-L1之间的结合亲和力。
图163示出了根据本发明实施方式获得的GI-101_P41融合蛋白与IL-2Rβ、CTLA-4或PD-L1之间的结合亲和力。
图164示出了根据本发明实施方式获得的GI-101_P42融合蛋白与IL-2Rβ、CTLA-4或PD-L1之间的结合亲和力。
图165示出了根据本发明实施方式获得的GI-101_P43融合蛋白与IL-2Rβ、CTLA-4或PD-L1之间的结合亲和力。
图166示出了根据本发明实施方式获得的GI-101_P44融合蛋白与IL-2Rβ、CTLA-4或PD-L1之间的结合亲和力。
图167示出了根据本发明实施方式获得的GI-101_P45融合蛋白与IL-2Rβ、CTLA-4或PD-L1之间的结合亲和力。
图168示出了根据本发明实施方式获得的GI-101_P46融合蛋白与IL-2Rβ、CTLA-4或PD-L1之间的结合亲和力。
图169示出了根据本发明实施方式获得的GI-101_P47融合蛋白与IL-2Rβ、CTLA-4或PD-L1之间的结合亲和力。
图170示出了根据本发明实施方式获得的GI-101_P49融合蛋白与IL-2Rβ、CTLA-4或PD-L1之间的结合亲和力。
最佳具体实施方式
包含IL-2蛋白和CD80蛋白片段或其变体的融合蛋白
在本发明的一个方面，提供了一种融合蛋白，其包含IL-2蛋白和CD80蛋白片段或其变体。
IL-2蛋白
如本文所用，除非另有说明，否则术语“IL-2”或“白细胞介素-2”是指从任何脊椎动物来源获得的任何野生型IL-2，脊椎动物包括哺乳动物，例如灵长类动物(如人类)和啮齿动物(如小鼠和大鼠)。IL-2可以从动物细胞中获得，也包括从能够产生IL-2的重组细胞中获得的IL-2。此外，IL-2可以是野生型IL-2或其变体。
在本说明书中，IL-2或其变体可以统一用术语“IL-2蛋白”或“IL-2多肽”来表示。IL-2、IL-2蛋白、IL-2多肽和IL-2变体特异性结合例如IL-2受体。这种特异性结合可以通过本领域技术人员已知的方法来鉴定。
IL-2的实施方式可以具有SEQ ID NO:35或SEQ ID NO:36的氨基酸序列。在这里，IL-2也可以是成熟形式。具体而言，成熟的IL-2可以不包含信号序列，并且可以具有SEQ IDNO:10的氨基酸序列。在这里，IL-2可以在涵盖野生型IL-2的片段的概念下使用，其中野生型IL-2的N端或C端的部分被截短。
此外，IL-2的片段可以是从具有SEQ ID NO:35或SEQ ID NO:36的氨基酸序列的蛋白质的N端截短1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24或25个连续氨基酸的形式。此外，IL-2的片段可以是从具有SEQ ID NO:35或SEQ ID NO:36的氨基酸序列的蛋白质的C端被截短1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24或25个连续氨基酸的形式。
如本文所用，术语“IL-2变体”是指全长IL-2或IL-2的上述片段中的部分氨基酸被取代的形式。也就是说，IL-2变体可以具有不同于野生型IL-2或其片段的氨基酸序列。然而，IL-2变体可具有与野生型IL-2相当或相似的活性。在这里，“IL-2活性”例如可以指与IL-2受体的特异性结合，该特异性结合可以通过本领域技术人员已知的方法来测量。
具体而言，可以通过取代野生型IL-2中的部分氨基酸来获得IL-2变体。通过氨基酸取代获得的IL-2变体的实施方式可以通过取代SEQ ID NO:10的氨基酸序列中的第38、42、45、61和72位氨基酸中的至少一个而获得。
具体地，IL-2变体可以通过用另一种氨基酸取代SEQ ID NO:10的氨基酸序列中的第38、42、45、61或72位氨基酸中的至少一个而获得。此外，当IL-2是SEQ ID NO:35的氨基酸序列中的N端的部分被截短的形式时，与SEQ ID NO:10的氨基酸序列中的位置互补对应的位置处的氨基酸可以被另一种氨基酸取代。例如，当IL-2具有SEQ ID NO:35的氨基酸序列时，其IL-2变体可以通过用另一种氨基酸取代SEQ ID NO:35的氨基酸序列中的第58、62、65、81或92位氨基酸中的至少一个而获得。这些氨基酸残基分别对应于SEQ ID NO:10的氨基酸序列中的第38、42、45、61和72位氨基酸残基。根据一个实施方式，一个、两个、三个、四个、五个、六个、七个、八个、九个或十个氨基酸可以被取代，只要这样的IL-2变体保持IL-2活性。根据另一个实施方式，可以取代一个至五个氨基酸。
在一个实施方式中，IL-2变体可以是两个氨基酸被取代的形式。具体地，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第38和42位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第38和45位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第38和61位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第38和72位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第42和45位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第42和61位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第42和72位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第45和61位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第45和72位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第61和72位氨基酸来获得。
此外，IL-2变体可以是三个氨基酸被取代的形式。具体地，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第38、42和45位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第38、42和61位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第38、42和72位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第38、45和61位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第38、45和72位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第38、61和72位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第42、45和61位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第42、45和72位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第45、61和72位氨基酸来获得。
此外，IL-2变体可以是其中四个氨基酸被取代的形式。具体地，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第38、42、45和61位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第38、42、45和72位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第38、45、61和72位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ IDNO:10的氨基酸序列中的第38、42、61和72位氨基酸来获得。此外，在一个实施方式中，IL-2变体可以通过取代SEQ ID NO:10的氨基酸序列中的第42、45、61和72位氨基酸来获得。
此外，IL-2变体可以是五个氨基酸被取代的形式。具体地，IL-2变体可以通过用另一种氨基酸取代SEQ ID NO:10的氨基酸序列中的第38、42、45、61和72位氨基酸中的每个而获得。
在这里，通过取代引入的“另一种氨基酸”可以是选自由以下组成的组中的任意一种氨基酸：丙氨酸、精氨酸、天冬酰胺、天冬氨酸、半胱氨酸、谷氨酸、谷氨酰胺、组氨酸、异亮氨酸、亮氨酸、赖氨酸、蛋氨酸、苯丙氨酸、脯氨酸、丝氨酸、苏氨酸、色氨酸、酪氨酸和缬氨酸。然而，关于IL-2变体的氨基酸取代，在SEQ ID NO:10的氨基酸序列中，第38位氨基酸不能被精氨酸取代，第42位氨基酸不能被苯丙氨酸取代，第45位氨基酸不能被酪氨酸取代，第61位氨基酸不能被谷氨酸取代，以及第72位氨基酸不能被亮氨酸取代。
关于IL-2变体的氨基酸取代，在SEQ ID NO:10的氨基酸序列中，第38位氨基酸精氨酸可以被精氨酸以外的氨基酸取代。优选地，关于IL-2变体的氨基酸取代，在SEQ ID NO:10的氨基酸序列中，第38位氨基酸精氨酸可以被丙氨酸(R38A)取代。
关于IL-2变体的氨基酸取代，在SEQ ID NO:10的氨基酸序列中，第42位氨基酸苯丙氨酸可以被苯丙氨酸以外的氨基酸取代。优选地，关于IL-2变体的氨基酸取代，在SEQ IDNO:10的氨基酸序列中，第42位氨基酸苯丙氨酸可以被丙氨酸(F42A)取代。
关于IL-2变体的氨基酸取代，在SEQ ID NO:10的氨基酸序列中，第45位氨基酸酪氨酸可以被酪氨酸以外的氨基酸取代。优选地，关于IL-2变体的氨基酸取代，在SEQ ID NO:10的氨基酸序列中，第45位氨基酸酪氨酸可以被丙氨酸(Y45A)取代。
关于IL-2变体的氨基酸替换，在SEQ ID NO:10的氨基酸序列中，第61位氨基酸谷氨酸可以被谷氨酸以外的氨基酸取代。优选地，关于IL-2变体的氨基酸取代，在SEQ ID NO:10的氨基酸序列中，第61位氨基酸谷氨酸可以被精氨酸(E61R)取代。
关于IL-2变体的氨基酸取代，在SEQ ID NO:10的氨基酸序列中，第72位氨基酸亮氨酸可以被亮氨酸以外的氨基酸取代。优选地，关于IL-2变体的氨基酸取代，在SEQ ID NO:10的氨基酸序列中，第72位氨基酸亮氨酸可以被甘氨酸(L72G)取代。
具体地，IL-2变体可以通过在SEQ ID NO:10的氨基酸序列中进行选自由R38A、F42A、Y45A、E61R和L72G组成的组中的至少一个取代而获得。
具体地，IL-2变体可以通过在选自由R38A、F42A、Y45A、E61R和L72G组成的组中的位置中的两个、三个、四个或五个位置处的氨基酸取代而获得。
此外，IL-2变体可以是两个氨基酸被取代的形式。具体地，IL-2变体可以通过取代R38A和F42A获得。此外，在一个实施方式中，IL-2变体可以通过取代R38A和Y45A获得。此外，在一个实施方式中，IL-2变体可以通过取代R38A和E61R获得。此外，在一个实施方式中，IL-2变体可以通过取代R38A和L72G获得。此外，在一个实施方式中，IL-2变体可以通过取代F42A和Y45A获得。此外，在一个实施方式中，IL-2变体可以通过取代F42A和E61R获得。此外，在一个实施方式中，IL-2变体可以通过取代F42A和L72G获得。此外，在一个实施方式中，IL-2变体可以通过取代E61R和L72G获得。
此外，IL-2变体可以是三个氨基酸被取代的形式。具体地，IL-2变体可以通过取代R38A、F42A和Y45A获得。此外，在一个实施方式中，IL-2变体可以通过取代R38A、F42A和E61R获得。此外，在一个实施方式中，IL-2变体可以通过取代R38A、F42A和L72G获得。此外，在一个实施方式中，IL-2变体可以通过取代R38A、Y45A和E61R获得。此外，在一个实施方式中，IL-2变体可以通过取代R38A、Y45A和L72G获得。此外，在一个实施方式中，IL-2变体可以通过取代F42A、Y45A和E61R获得。此外，在一个实施方式中，IL-2变体可以通过取代F42A、Y45A和L72G获得。此外，在一个实施方式中，IL-2变体可以通过取代F42A、E61R和L72G获得。此外，在一个实施方式中，IL-2变体可以通过取代Y45A、E61R和L72G获得。
此外，IL-2变体可以是四个氨基酸被取代的形式。具体地，IL-2变体可通过取代R38A、F42A、Y45A和E61R获得。此外，在一个实施方式中，IL-2变体可以通过取代R38A、F42A、Y45A和L72G获得。此外，在一个实施方式中，IL-2变体可以通过取代R38A、F42A、E61R和L72G获得。此外，在一个实施方式中，IL-2变体可以通过取代R38A、Y45A、E61R和L72G获得。此外，在一个实施方式中，IL-2变体可以通过取代F42A、Y45A、E61R和L72G获得。
此外，IL-2变体可以通过取代R38A、F42A、Y45A、E61R和L72G获得。
优选地，IL-2变体的一个实施方式可以包括在SEQ ID NO:10的氨基酸序列中进行选自以下取代组合(a)至(d)中的任意一种：
(a)R38A/F42A
(b)R38A/F42A/Y45A
(c)R38A/F42A/E61R
(d)R38A/F42A/L72G。
在这里，当IL-2具有SEQ ID NO:35的氨基酸序列时，氨基酸取代可以存在于与SEQID NO:10的氨基酸序列中的位置互补对应的位置。此外，即使当IL-2是SEQ ID NO:35的氨基酸序列的片段时，氨基酸取代也可以存在于与SEQ ID NO:10的氨基酸序列中的位置互补对应的位置。
具体地，IL-2变体可具有SEQ ID NO:6、22、23或24的氨基酸序列。
此外，IL-2变体的特征可以在于具有低体内毒性。在这里，低体内毒性可能是由IL-2与IL-2受体α链(IL-2Rα)结合引起的副作用。已经开发了各种IL-2变体以改善由IL-2与IL-2Rα结合引起的副作用，并且此类IL-2变体可以是美国专利号5,229,109和韩国专利号1667096中公开的那些。特别地，本申请中描述的IL-2变体对IL-2受体α链(IL-2Rα)的结合能力低，因此具有比野生型IL-2更低的体内毒性。
CD80蛋白片段或其变体
如本文所用，术语“CD80”，也称为“B7-1”，是存在于树突细胞、活化的B细胞和单核细胞中的膜蛋白。CD80提供对T细胞的活化和存活至关重要的共刺激信号。CD80被认为是存在于T细胞表面的两种不同蛋白质CD28和CTLA-4的配体。CD80由288个氨基酸组成，并且具体可具有SEQ ID NO:11的氨基酸序列。另外，如本文所用，术语“CD80蛋白”是指全长CD80或CD80片段。
如本文所用，术语“CD80片段”是指CD80的切割形式。此外，CD80片段可以是CD80的细胞外结构域。CD80片段的实施方式可以通过去除作为CD80的信号序列的从N端开始的第1至34位氨基酸而获得。具体地，CD80片段的实施方式可以是由SEQ ID NO:11中的第35至288位氨基酸组成的蛋白质。此外，CD80片段的实施方式可以是由SEQ ID NO:11中的第35至242位氨基酸组成的蛋白质。此外，CD80片段的实施方式可以是由SEQ ID NO:11中的第35至232位氨基酸组成的蛋白质。此外，CD80片段的实施方式可以是由SEQ ID NO:11中的第35至139位氨基酸组成的蛋白质。此外，CD80片段的实施方式可以是由SEQ ID NO:11中的第142至242位氨基酸组成的蛋白质。在实施方式中，CD80片段可以具有SEQ ID NO:2的氨基酸序列。
此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第35至231位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第35至224位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第35至219位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第35至211位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第35至208位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第35至196位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ IDNO:11中的第35至192位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQID NO:11中的第35至184位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第35至145位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第41至145位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第46至145位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第55至145位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第61至145位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第61至138位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第78至145位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第61至84位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第61至77位氨基酸组成的蛋白质。此外，CD80蛋白片段的实施方式可以是由SEQ ID NO:11中的第112至138位氨基酸组成的蛋白质。
此外，CD80蛋白片段的变体可以是包括IgV结构域或其片段、IgC结构域或其片段或这两者的变体CD80多肽。具体而言，CD80蛋白片段的变体意味着构成它的氨基酸中的一个或多个已被另一种氨基酸取代。具体地，在SEQ ID NO:2的氨基酸中，第4、9、10、11、12、13、14、15、16、17、18、20、21、22、24、25、27、28、29、30、31、33、36、37、38、40、41、42、43、44、47、48、50、52、53、54、59、60、61、62、63、64、65、66、67、68、69、70、72、74、76、77、80、81、83、85、86、87、88、89、90、91、92、93、94、95、96、97、99、102、103、104、107、108、109、110、114、115、116、117、118、120、121、122、126、127、128、129、130、133、137、140、142、143、144、148、149、152、154、160、162、164、168、169、174、175、177、178、183、185、188、190、192、193或199位氨基酸可以被另一种氨基酸取代。
具体地，CD80蛋白片段的变体的一个或多个氨基酸取代可以是V4M、K9E、E10R、V11S、A12G、A12T、A12V、T13N、L14A、S15V、S15F、C16S、C16G、C16L、G17W、H18L、H18R、H18Y、V20L、S21P、V22A、E24G、L25P、Q27R、T28A、T28S、R29C、R29D、R29H、R29V、I30V、Y31F、Y31H、Y31L、Q33H、K36E、K36G、K37E、K37Q、M38I、M38L、M38T、M38V、L40M、T41A、T41G、T41D、T41I、M42T、M43I、M43Q、M43R、M43V、S44P、M47T、N48D、N48I、W50G、E52G、Y53C、K54M、F59L、F59S、D60V、I61N、T62S、N63S、N64S、L65H、S66H、I67F、I67T、V68A、V68M、I69T、L70Q、L70P、L70R、L72P、P74L、D76G、E77G、E77K、Y80N、E81A、E81R、E81V、V83A、V83I、L85I、L85R、K86E、Y87N、E88D、E88G、K89E、K89N、K89R、D90K、D90L、D90N、A91E、A91G、A91S、A91T、F92L、F92N、F92P、F92Y、K93I、K93E、K93Q、K93R、K93V、R94G、R94L、R94F、E95K、H96R、L97R、E99D、E99G、L102S、S103L、S103P、V104A、V104L、D107N、F108L、P109S、P109H、T110A、S114T、D115G、F116S、F116L、E117V、E117G、I118V、I118A、I118T、T120S、S121P、N122S、I126L、I126V、I127T、C128Y、C128R、S129L、S129P、T130A、G133D、P137L、S140T、L142S、E143G、N144D、N144S、L148S、N149D、N149S、N152T、T154I、T154A、E160G、E162G、Y164H、S168G、K169E、K169I、K169S、M174T、M174V、T175A、N177S、H178R、L183H、K185E、H188D、H188Q、R190S、N192D、Q193L、T199S或其保守氨基酸取代。
更具体地，取代的变体可以是V4M/L70Q/A91G/T120S/T130A、A12T/H18L/M43V/F59L/E77K/P109S/I118T、A12V/S15F/Y31H/T41G/T130A/P137L/N152T、V20L/L70Q/A91S/T120S/T130A、V22A/L70Q/S121P、E24G/L25P/L70Q/T120S、T28S/L70Q/A91G/E95K/T120S/T130A、E24G/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/F59L/E81V/L85R/K89N/A91T/F92P/K93V/R94L/H96R、R29D/Y31L/Q33H/K36G/M38I/T41A/M42T/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/L148S/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/N144S/N149S、R29H/Y31H/T41G/Y87N/E88G/K89E/D90N/A91G/P109S、R29H/E52G/L70R/E88G/A91G/T130A、R29H/E52G/T120S/T130A、R29V/Y31F/K36G/M38L/M43Q/E81R/V83I/L85I/K89R/D90L/A91E/F92N/K93Q/R94G、R29V/M43Q/E81R/L85I/K89R/D90L/A91E/F92N/K93Q/R94G、Y31H/T41G/L70Q/A91G/T120S/T130A、K36G、K36G/K37Q/M38I/L40M、K36G/K37Q/M38I/F59L/E81V/L85R/K89N/A91T/F92P/K93V/R94L/E99G/T130A/N149S、K36E/I67T/L70Q/A91G/T120S/T130A/N152T、K37E/F59S/L70Q/A91G/T120S/T130A、M38T/L70Q/E77G/A91G/T120S/T130A/N152T、M38V/T41D/M43I/W50G/D76G/V83A/K89E/T120S/T130A、T41I/A91G、S44P/L70Q/A91G/T130A、E52G/L70Q/A91G/T120S/T130A、K54M/A91G/T120S、D60V/A91G/T120S/T130A、N63S/L70Q/A91G/T120S/T130A、S66H/D90G/T110A/F116L、I67F/L70R/E88G/A91G/T120S/T130A、I67T/L70Q/A91G/T120S、V68A/T110A、V68M/L70P/L72P/K86E、L70Q/A91G/T110A/T120S/T130A、L70Q/E81A/A91G/T120S/I127T/T130A、L70Q/Y87N/A91G/T130A、L70Q/A91G、L70Q/A91G/E117G/T120S/T130A、L70Q/A91G/T120S/T130A、L70Q/A91G/T130A、L70Q/A91G/I118A/T20S/T130A、L70R/A91G/T120S/T130A、E88D/K89R/D90K/A91G/F92Y/K93R、K89E/T130A、K89R/D90K/A91G/F92Y/K93R、E88D/K89R/D90K/A91G/F92Y/K93R/N122S/N177S、K89R/D90K/A91G/F92Y/K93R/N122S/N177S、A91G、A91G/F92L/F108L/T120S、A91G/L102S、A91G/S103P、A91G/T120S/T130A、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/I127T/T130A/K169E、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/I127T/T130A、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/I127T/T130A/K169E、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/T130A/M174T、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/F59L/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/I127T/T130A/H188D、H18R/R29D/Y31L/Q33H/K36G/K37E/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/T130A/K169E/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/I127T/T130A/E143G/K169E/M174V/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/I127T/T130A、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/I127T/T130A/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/I127T/T130A/K169E、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/I127T/T130A、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L85R/K89N/A91T/F92P/K93V/R94L/T120S/I127T/T130A/K169E/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/F108L/T120S/T130A/K169E/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T130A/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/I127T/T130A/K169E、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/T130A/K169E/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/I127T/C128Y/T130A/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94F/T130A/K169E、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T130A、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/T130A/K169E、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93I/R94L/L97R/T130A、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93I/R94L/L97R/T130A/L148S、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A/K169E、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/I61N/E81V/L85R/K89N/A91T/F92P/K93V/R94F/V104A/T120S/T130A、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/F92P/K93V/R94F/I118V/T130A、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/T62S/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/T130A/K169E/T175A、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/F116S/T130A/H188D、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/I127T/T130A/L142S/H188D、C16S/H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T110A/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/A91G/T120S/I127T/T130A/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/D76G/A91G/S103L/T120S/I127T/T130A、Q33deleted/Y53C/L85R/K89N/A91T/F92P/K93V/R94L/T120S/I127T/T130A/K169E、T62S/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T120S/T130A/K169E、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/S129L/H188D、K9E/E10R/V11S/A12G/T13N/K14A/S15V/C16L/G17W/H18Y/Y53C/L70Q/D90G/T130A/N149D/N152T/H188D、H18L/R29D/Y31L/Q33H/K36G/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A/H188D、K89E/K93E/T130A、S21P/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/N48I/V68A/E81V/L85R/K89N/A91T/F92P/K93V/R94L/P109H/I126L/K169I、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/P74L/Y80N/E81V/L85R/K89N/A91T/F92P/K93V/R94L/L97R、S21P/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/P74L/Y80N/E81V/L85R/K89N/D90N/A91T/F92P/K93V/R94L/T130A/N149S/E162G、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/V68M/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T130A、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/V68M/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T130A/N149S/R190S、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/P74L/Y80N/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T130A/R190S、C16G/V22A/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/V68M/D76G/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/T130A/S140T/N149S/K169I/H178R/N192D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94F/E117V/I118T/N149S/S168G/H188Q、V22A/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/V68M/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T130A、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/N64S/E81V/L85R/K89N/A91T/F92P/K93V/R94F/I118T/T130A/N149S/K169I、V22A/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/V68M/E81V/L85R/K89N/A91T/F92P/K93V/R94L/D115G/I118T/T130A/G133D/N149S、S129P、A91G/S129P、I69T/L70Q/A91G/T120S、Y31H/S129P、T28A/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/V104L/T130A/N149S、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/L97R/N149S/H188Q、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/L97R/N149S、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/V68A/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T130A/N149S/T154I、A12G/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/V68A/E81V/L85R/K89N/A91T/F92P/K93V/R94L/L97R/T130A/L183H、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/T130A/S140T/N149S/K169S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/T130A/N149S/K169I/Q193L、V22A/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/T130A/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/T130A/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/T130A/N149S/K169I、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94F/T130A/N149S/K169I、I118T/C128R、Q27R/R29C/M42T/S129P/E160G、S129P/T154A、S21P/L70Q/D90G/T120S/T130A、L70Q/A91G/N144D、L70Q/A91G/I118A/T120S/T130A/K169E、V4M/L70Q/A91G/I118V/T120S/T130A/K169E、L70Q/A91G/I118V/T120S/T130A/K169E、L70Q/A91G/I118V/T120S/T130A、V20L/L70Q/A91S/I118V/T120S/T130A、L70Q/A91G/E117G/I118V/T120S/T130A、A91G/I118V/T120S/T130A、L70R/A91G/I118V/T120S/T130A/T199S、L70Q/E81A/A91G/I118V/T120S/I127T/T130A、T28S/L70Q/A91G/E95K/I118V/T120S/I126V/T130A/K169E、N63S/L70Q/A91G/S114T/I118V/T120S/T130A、K36E/I67T/L70Q/A91G/I118V/T120S/T130A/N152T、E52G/L70Q/A91G/D107N/I118V/T120S/T130A/K169E、K37E/F59S/L70Q/A91G/I118V/T120S/T130A/K185E、D60V/A91G/I118V/T120S/T130AK169E、K54M/L70Q/A91G/Y164H/T120S、M38T/L70Q/E77G/A91G/I118V/T120S/T130A/N152T、Y31H/T41G/M43L/L70Q/A91G/I118V/T120S/I126V/T130A、L65H/D90G/T110A/F116L、R29H/E52G/D90N/I118V/T120S/T130A、I67T/L70Q/A91G/I118V/T120S、L70Q/A91G/T110A/I118V/T120S/T130A、M38V/T41D/M43I/W50G/D76G/V83A/K89E/I118V/T120S/I126V/T130A、A12V/S15F/Y31H/M38L/T41G/M43L/D90N/T130A/P137L/N149D/N152T、I67F/L70R/E88G/A91G/I118V/T120S/T130A、E24G/L25P/L70Q/A91G/I118V/T120S/N152T、A91G/F92L/F108L/I118V/T120S、E88D/K89R/D90K/A91G/F92Y/K93R/N122S/N177S、K36G/K37Q/M38I/L40M/F59L/E81V/L85R/K89N/A91T/F92P/K93V/R94L/E99G/T130A/N149S、K36G/L40M、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A/K169E、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A/K169E、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/T130A/K169E/M174T、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/N48D/F59L/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A/H188D、H18R/R29D/Y31L/Q33H/K36G/K37E/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/T130A/K169E/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A/E143G/K169E/M174V/H188D、R29D/I30V/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A/K169E、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A/K169E/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/F108L/I118V/T120S/T130A/K169E/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/T130A/N149D/K169E/H188D、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/T130A/K169E/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/C128Y/T130A/H188D、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/E99D/T130A、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/T130A/K169E、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/I61N/E81V/L85R/K89N/A91T/F92P/K93V/R94F/V104A/I118V/T120S/I126V/T130A、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94F/I118V/T120S/T130A、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A/L142S/H188D、C16S/H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T110A/I118V/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/A91G/I118V/T120S/I127T/T130A/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/L70Q/D76G/A91G/S103L/I118V/T120S/I127T/T130A、Y53C/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A/K169E、T62S/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/T130A/K169E、Y53C/L70Q/D90G/T130A/N149D/N152T/H188D、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A/H188D、或H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T130A/N149S。
此外，CD80变体的实施方式可以是选自由以下组成的组中的任一种：A12T、H18L、V20L、R29H、Y31H、K36G、T41G、T41I、M43V、E52G、F59L、D60V、N63S、I67T、L70Q、L70R、E77K、E81A、Y87N、E88D、E88G、K89E、K89R、D90K、D90N、L40M、A91G、A91S、F92Y、K93R、D107N、P109S、S114T、E117G、I118A、I118T、I118V、T120S、I127T、T130A、N144D、K169E、N177S、和T199S，以及其保守氨基酸取代。
具体地，变体的一个或多个氨基酸取代可以是A12T/H18L/M43V/F59L/E77K/P109S/I118T、V20L/L70Q/A91S/T120S/T130A、V20L/L70Q/A91S/I118V/T120S/T130A、R29H/Y31H/T41G/Y87N/E88G/K89E/D90N/A91G/P109S、K36G、K36G/L40M、T41I/A91G、E52G/L70/A91G/T120S/T130A、E52G/L70Q/A91G/D107N/I118V/T120S/T130A/K169E、D60V/A91G/T120S/T130A、D60V/A91G/I118V/T120S/T130A/K169E、N63S/L70Q/A91G/T120S/T130A、N63S/L70Q/A91G/S114T/I118V/T120S/T130A、I67T/L70Q/A91G/T120S、I67T/L70Q/A91G/I118V/T120S、L70Q/E81A/A91G/T120S/I127T/T130A、L70Q/E81A/A91G/I118V/T120S/I127T/T130A、L70Q/Y87N/A91G/T130A、L70Q/A91G、L70Q/A91G/N144D、L70Q/A91G/E117G/T120S/T130A、L70Q/A91G/E117G/I118V/T120S/T130A、L70Q/A91G/I118A/T120S/T130A、L70Q/A91G/I118A/T120S/T130A/K169E、L70Q/A91G/T120S/T130A、L70R/A91G/T120S/T130A、L70R/A91G/I118V/T120S/T130A/T199SL70Q/A91G/I118V/T120S/T130A/K169E、E88D/K89R/D90K/A91G/F92Y/K93R、K89R/D90K/A91G/F92Y/K93R、E88D/K89R/D90K/A91G/F92Y/K93R/N122S/N177S、或K89R/D90K/A91G/F92Y/K93R/N122S/N177S。
此外，CD80变体的一个或多个氨基酸取代可以选自由以下组成的组：A12G、A12T、H18L、S21P、V22A、T28A、R29D、R29H、Y31H、Y31L、Q33H、K36G、M38I、M38L、L40M、T41A、T41G、M42T、M43R、M43V、M47T、N48I、F59L、N64S、I67T、V68A、V68M、L70Q、E77K、E81V、L85R、Y87N、E88D、E88G、K89E、K89N、K89R、D90K、D90N、A91G、A91T、F92P、F92Y、K93E、K93V、R94F、R94L、L97R、S103L、S103P、V104L、P109H、P109S、D115G、E117V、I118T、I118V、T120S、N122S、I126L、T130A、G133D、S140T、N144S、L148S、N149S、S168G、K169I、K169S、N177S、L183H、H188Q、R190S和Q193L以及其保守氨基酸取代。
具体地，CD80变体的一个或多个氨基酸取代可以是A12T/H18L/M43V/F59L/E77K/P109S/I118T、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/N144S/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M42T/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/L148S/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/N149S、R29H/Y31H/T41G/Y87N/E88G/K89E/D90N/A91G/P109S、K36G、K36G/L40M、I67T/L70Q/A91G/T120S、I67T/L70Q/A91G/I118V/T120S、E88D/K89R/D90K/A91G/F92Y/K93R、K89R/D90K/A91G/F92Y/K93R、A91G、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/N144S/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M42T/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/L148S/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/N149S、R29H/Y31H/T41G/Y87N/E88G/K89E/D90N/A91G/P109S、K36G、K36G/L40M、I67T/L70Q/A91G/T120S、I67T/L70Q/A91G/I118V/T120S、E88D/K89R/D90K/A91G/F92Y/K93R、K89R/D90K/A91G/F92Y/K93R、A91G、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118V/T120S/I127T/T130A/H188D、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/V68M/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T130A/N149S/R190S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94F/E117V/I118T/N149S/S168G/H188Q、V22A/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/V68M/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T130A、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/N64S/E81V/L85R/K89N/A91T/F92P/K93V/R94F/I118T/T130A/N149S/K169I、V22A/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/V68M/E81V/L85R/K89N/A91T/F92P/K93V/R94L/D115G/I118T/T130A/G133D/N149S、T28A/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/V104L/T130A/N149S、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/L97R/N149S/H188Q、K89E/T130A、K89E/K93E/T130A、S21P/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/N48I/V68A/E81V/L85R/K89N/A91T/F92P/K93V/R94L/S21P/N48I/V68A/P109H/I126L/K169I、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/V68M/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T130A、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/T130A/N149S、A12G/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/V68A/E81V/L85R/K89N/A91T/F92P/K93V/R94L/L97R/T130A/L183H、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/T130A/S140T/N149S/K169S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/T130A/N149S/K169I/Q193L、V22A/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/T130A/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/T130A/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/T130A/N149S/K169I、或R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94F/T130A/N149S/K169I。
此外，CD80变体的一个或多个氨基酸取代可以选自由以下组成的组：A12T、H18L、K36G、L40M、M43V、F59L、E77K、E88D、K89R、D90K、A91G、F92Y、K93R、P109S、I118T、N112S、N177S以及其保守氨基酸取代。
具体地，CD80变体的一个或多个氨基酸取代可以是A12T/H18L/M43V/F59L/E77K/P109S/I118T、K36G、K36G/L40M、E88D/K89R/D90K/A91G/F92Y/K93R、K89R/D90K/A91G/F92Y/K93R、E88D/K89R/D90K/A91G/F92Y/K93R/N122S/N177S、或K89R/D90K/A91G/F92Y/K93R/N122S/N177S。
此外，CD80变体的一个或多个氨基酸取代可以选自由以下组成的组：V4M、R29H、Y31H、K36G、L40M、T41G、E52G、I67T、V68A、L70Q、Y87N、E88D、E88G、K89E、K89R、D90K、D90N、A91G、F92Y、K93R、D107N、P109S、T110A、I118V、T120S、T130A、N144D、和K169E，以及其保守氨基酸取代。
具体地，CD80变体的一个或多个氨基酸取代可以是V4M/L70Q/A91G/T120S/T130A、V4M/L70Q/A91G/I118V/T120S/T130A/K169E、R29H/Y31H/T41G/Y87N/E88G/K89E/D90N/A91G/P109S、K36G、K36G/L40M、E52G/L70Q/A91G/T120S/T130A、E52G/L70Q/A91G/D107N/I118V/T120S/T130A/K169E、I67T/L70Q/A91G/T120S、I67T/L70Q/A91G/I118V/T120S,V68A/T110A、L70Q/A91G、L70Q/A91G/N144D、L70Q/A91G/T120S/T130A、L70Q/A91G/I118V/T120S/T130A/K169E、L70Q/A91G/T130A、K89R/D90K/A91G/F92Y/K93R、E88D/K89R/D90K/A91G/F92Y/K93R、A91G/I118V/T120S/T130A、A91G/T120S/T130A、或I69T/L70Q/A91G/T120S。
此外，CD80变体的一个或多个氨基酸取代可以选自由以下组成的组：K36G、L40M、E52G、L70Q、E88D、K89R、D90K、A91G、F92Y、K93R、D107N、I118V、T120S、T130A、N144D、和K169E，以及其保守氨基酸取代。
具体地，CD80变体的一个或多个氨基酸取代可以是K36G、K36G/L40M、E52G/L70Q/A91G/T120S/T130A、E52G/L70Q/A91G/D107N/I118V/T120S/T130A/K169E、L70Q/A91G、L70Q/A91G/N144D、L70Q/A91G/T120S/T130A、L70Q/A91G/I118V/T120S/T130A/K169E、E88D/K89R/D90K/A91G/F92Y/K93R、或K89R/D90K/A91G/F92Y/K93R。
此外，CD80变体的一个或多个氨基酸取代可以选自由以下组成的组：R29H、Y31H、K36G、L40M、T41G、I67T、L70Q、Y87N、E88D、E88G、K89E、K89R、D90N、D90K、A91G、F92Y、K93R、P109S、I118V、T120S，以及其保守氨基酸取代。
具体地，CD80变体的一个或多个氨基酸取代可以是R29H/Y31H/T41G/Y87N/E88G/K89E/D90N/A91G/P109S、K36G、K36G/L40M、I67T/L70Q/A91G/T120S、I67T/L70Q/A91G/I118V/T120S、E88D/K89R/D90K/A91G/F92Y/K93R、或K89R/D90K/A91G/F92Y/K93R。
此外，CD80变体的一个或多个氨基酸取代可以选自由以下组成的组：K36G、L40M、E88D、K89R、D90K、A91G、F92Y、K93R，以及其保守氨基酸取代。
具体地，CD80变体的一个或多个氨基酸取代可以是K36G、K36G/L40ME88D/K89R/D90K/A91G/F92Y/K93R、或K89R/D90K/A91G/F92Y/K93R。
此外，CD80变体的一个或多个氨基酸取代可以选自由以下组成的组：R29D、R29H、Y31H、Y31L、Q33H、K36G、M38I、T41A、T41G、M42T、M43R、M47T、N63S、I67T、L70Q、E81A、E81V、L85R、Y87N、E88G、K89E、K89N、D90N、A91G、A91T、F92P、K93V、R94L、P109S、S114T、I118T、I118V、T120S、I127T、T130A、N144S、L148S、和N149S，以及其保守氨基酸取代。
具体地，CD80变体的一个或多个氨基酸取代可以是N63S/L70Q/A91G/T120S/T130A、N63S/L70Q/A91G/S114T/I118V/T120S/T130A、或L70Q/Y87N/A91G/T120S/I127T/T130A。
此外，CD80变体的一个或多个氨基酸取代可以选自由以下组成的组：N63S、L70Q、E81A、Y87N、A91G、S114T、I118V、T120S、I127T、和T130A，以及其保守氨基酸取代。
具体地，CD80变体的一个或多个氨基酸取代可以是R29D/Y31L/Q33H/K36G/M38I/T41A/M42T/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/L148S/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/N144S/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/N149S、R29H/Y31H/T41G/Y87N/E88G/K89E/D90N/A91G/P109S、N63S/L70Q/A91G/T120S/T130A、N63S/L70Q/A91G/S114T/I118V/T120S/T130A、I67T/L70Q/A91G/T120S、I67T/L70Q/A91G/I118V/T120S、或L70Q/Y87N/A91G/T120S/I127T/T130A。
此外，CD80变体的一个或多个氨基酸取代可以选自由以下组成的组：R29D、R29H、Y31H、Y31L、Q33H、K36G、M38I、T41A、T41G、M42T、M43R、M47T、I67T、L70Q、E81V、L85R、Y87N、E88G、K89E、K89N、D90N、A91G、A91T、F92P、K93V、R94L、P109S、I118T、I118V、T120S、N144S、L148S、和N149S，以及其保守氨基酸取代。
具体地，CD80变体的一个或多个氨基酸取代可以是R29D/Y31L/Q33H/K36G/M38I/T41A/M42T/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/L148S/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/I118T/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/N144S/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/N149S、R29H/Y31H/T41G/Y87N/E88G/K89E/D90N/A91G/P109S、I67T/L70Q/A91G/I118V/T120S或I67T/L70Q/A91G/T120S。
此外，CD80变体的一个或多个氨基酸取代可以选自由以下组成的组：L70Q、Y87N、A91G和T120S，以及其保守氨基酸取代。
在CD80变体的实施方式中，CD80蛋白片段的变体是至少一个氨基酸已被另一种氨基酸取代的变体。具体地，CD80蛋白片段的变体可以是选自由以下组成的组中的任一种：K89E/T130A、K89E/K93E/T130A、H18L/R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/L97R/T130A/N149S、R29D/Y31L/Q33H/K36G/M38I/T41A/M43R/M47T/E81V/L85R/K89N/A91T/F92P/K93V/R94L/A12G/V68A/L97R/T130A/L183H、A12G/H18L/V22A/N64S/V68M/T130A、和A12G/H18L/V22A/N64S/V68M/T130A。
此外，IL-2蛋白和CD80蛋白可以通过接头或载体彼此连接。具体地，IL-2或其变体和CD80(B7-1)或其片段可以通过接头或载体彼此连接。在本说明书中，接头和载体可以互换使用。
接头连接两个蛋白质。接头的实施方式可以包括1至50个氨基酸、白蛋白或其片段、免疫球蛋白的Fc结构域等。在这里，免疫球蛋白的Fc结构域是指含有免疫球蛋白的重链恒定区2(CH2)和重链恒定区3(CH3)并且不含免疫球蛋白的重链可变区、轻链可变区和轻链恒定区1(CH1)的蛋白质。免疫球蛋白可以是IgG、IgA、IgE、IgD或IgM，并且可以优选地是IgG4。在这里，野生型免疫球蛋白G4的Fc结构域可以具有SEQ ID NO:4的氨基酸序列。
此外，免疫球蛋白的Fc结构域可以是Fc结构域变体以及野生型Fc结构域。此外，如本文所用，术语“Fc结构域变体”可以指去糖基化形式，或，在糖基化模式方面与野生型Fc结构域不同、与野生型Fc结构域相比具有高糖基化、或与野生型Fc结构域相比具有低糖基化的形式。此外，其中包括非糖基化的Fc结构域。通过培养条件或对宿主的基因操纵，Fc结构域或其变体可适于具有调整后的数量的唾液酸、岩藻糖基化或糖基化。
此外，免疫球蛋白的Fc结构域的糖基化可以通过常规方法例如化学方法、酶方法和使用微生物的基因工程方法进行修饰。此外，Fc结构域变体可以是免疫球蛋白、IgG、IgA、IgE、IgD和IgM各自的Fc区的混合形式。此外，Fc结构域变体可以是Fc结构域的部分氨基酸被其他氨基酸取代的形式。Fc结构域变体的实施方式可以具有SEQ ID NO:12的氨基酸序列。
融合蛋白可以具有这样的结构：其中使用Fc结构域作为接头(或载体)，CD80蛋白和IL-2蛋白，或IL-2蛋白和CD80蛋白分别连接到接头或载体的N端和C端。Fc结构域的N端或C端与CD80或IL-2之间的连接可以可选地通过接头肽来实现。
具体地，融合蛋白可以由以下结构式(I)或(II)组成：
N'-X-[接头(1)]
N'-Y-[接头(1)]n-Fc结构域-[接头(2)]m-X-C'(II)
在这里，在所述结构式(I)和(II)中，
N'是融合蛋白的N端，
C'是融合蛋白的C端，
X是CD80蛋白，
Y是IL-2蛋白，
接头(1)和(2)是肽接头，以及
n和m各自独立地为0或1。
优选地，融合蛋白可以由结构式(I)组成。IL-2蛋白如上所述。此外，CD80片段或其变体如上所述。根据一个实施方式，IL-2蛋白可以是与野生型IL-2相比具有1至5个氨基酸取代的IL-2变体。CD80片段或其变体可以是通过从野生型CD80的N端或C端截短最多约34个连续氨基酸残基而获得的片段。可选择地，CD80蛋白可以是具有结合T细胞表面受体CTLA-4和CD28活性的细胞外免疫球蛋白样结构域。此外，CD80片段的变体如上所述。
具体地，融合蛋白可以具有SEQ ID NO:9、26、28或30的氨基酸序列。根据另一个实施方式，融合蛋白包括与SEQ ID NO:9、26、28或30的氨基酸序列具有85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％序列同一性的多肽。在这里，同一性例如是百分比同源性，并且可以通过同源性比较软件例如国家生物技术信息中心(NCBI)的BlastN软件来确定。
肽接头(1)可以包含在CD80蛋白和Fc结构域之间。肽接头(1)可由5至80个连续氨基酸、20至60个连续氨基酸、25至50个连续氨基酸或30至40个连续氨基酸组成。在一个实施方式中，肽接头(1)可以由30个氨基酸组成。此外，肽接头(1)可以包含至少一个半胱氨酸。具体地，肽接头(1)可以包含一个、两个或三个半胱氨酸。此外，肽接头(1)可以来源于免疫球蛋白的铰链。在一个实施方式中，肽接头(1)可以是由SEQ ID NO:3的氨基酸序列组成的肽接头。
肽接头(2)可由1至50个连续氨基酸、3至30个连续氨基酸或5至15个连续氨基酸组成。在一个实施方式中，肽接头(2)可以是(G4S)
在本发明的另一个方面，提供了通过结合两个融合蛋白获得的二聚体，两个融合蛋白各自包含IL-2蛋白和CD80蛋白片段或其变体。包含IL-2或其变体和CD80蛋白片段或其变体的融合蛋白如上所述。
在这里，构成二聚体的融合蛋白之间的结合可以通过但不限于由接头中存在的半胱氨酸形成的二硫键来实现。构成二聚体的融合蛋白可以是相同的融合蛋白，也可以是彼此不同的融合蛋白。优选地，二聚体可以是同型二聚体。构成二聚体的融合蛋白的实施方式可以是具有SEQ ID NO:9的氨基酸序列的蛋白质。
编码融合蛋白的多核苷酸
在本发明的又一个方面，提供了编码融合蛋白的多核苷酸，该融合蛋白包含IL-2蛋白和CD80蛋白片段或其变体。包含IL-2蛋白和CD80蛋白片段或其变体的融合蛋白如上所述。在多核苷酸中，一个或多个核苷酸可以通过取代、缺失、插入或其组合而改变。当通过化学合成制备核苷酸序列时，可以使用本领域公知的合成方法，例如在Engels和Uhlmann(Angew Chem IntEd Eng.,37:73-127,1988)中描述的那些。这样的方法可以包括三酯、亚磷酸盐、亚磷酰胺和H-磷酸盐方法、PCR和其他自引物(autoprimer)方法、在固体支持物上合成寡核苷酸等。
多核苷酸还可以包含编码信号序列或前导序列的核酸。如本文所用，术语“信号序列”是指引导目标蛋白分泌的信号肽。信号肽在宿主细胞中被翻译然后被切割。具体地，信号序列是起始蛋白质跨内质网(ER)膜迁移的氨基酸序列。在实施方式中，信号序列可以具有SEQ ID NO:1的氨基酸序列。
信号序列的特性在本领域中是众所周知的。此类信号序列通常包含16至30个氨基酸残基，并且可以包含比16至30个氨基酸残基更多或更少的氨基酸残基。典型的信号肽由三个区域组成，即碱性N端区域、中心疏水区域和更具极性的C端区域。中心疏水区域包含4至12个疏水残基，这些疏水残残基导致信号序列在未成熟多肽通过膜脂双层迁移期间被固定。
起始后，信号序列在ER腔内被细胞酶(通常称为信号肽酶)切割。在这里，信号序列可以是tPa(组织纤溶酶原活化物)、HSV gDs(单纯疱疹病毒糖蛋白D的信号序列)或生长激素的分泌信号序列。优选地，可以使用在高等真核细胞(括哺乳动物)等中使用的分泌信号序列。另外，可以使用包含在野生型IL-2和/或CD80中的信号序列，或者可以使用用在宿主细胞中具有高表达频率的密码子取代的信号序列。
具有编码融合蛋白的多核苷酸的运载体
在本发明的又一方面，提供了包含该多核苷酸的运载体。
可以将运载体导入宿主细胞以便与宿主细胞的基因组重组并插入宿主细胞的基因组中。此外，运载体被理解为含有可作为游离基因(episome)自主复制的多核苷酸序列的核酸工具。运载体包括线性核酸、质粒、噬菌粒、粘粒、RNA运载体、病毒运载体及其类似物。病毒运载体的实例包括但不限于逆转录病毒、腺病毒和腺相关病毒。
具体地，运载体可以包括质粒DNA、噬菌体DNA等；和商业开发的质粒(pUC18、pBAD、pIDTSAMRT-AMP等)、大肠杆菌来源的质粒(pYG601BR322、pBR325、pUC118、pUC119等)、枯草芽孢杆菌(Bacillus subtilis)来源的质粒(pUB110、pTP5等)、酵母来源的质粒(YEp13、YEp24、YCp50等)、噬菌体DNA(Charon4A、Charon21A、EMBL3、EMBL4、λgt10、λgt11、λZAP等)、动物病毒运载体(逆转录病毒、腺病毒、牛痘病毒等)、昆虫病毒运载体(杆状病毒等)。由于运载体取决于宿主细胞而表现出不同的表达水平和蛋白质的修饰，因此优选选择和使用最适合该目的的宿主细胞。
如本文所用，术语“基因表达”或目标蛋白的“表达”应理解为指DNA序列的转录、mRNA转录物的翻译和融合蛋白产物或其片段的分泌。有用的表达运载体可以是RcCMV(Invitrogen，Carlsbad)或其变体。表达运载体可以进一步包含用于促进目标基因在哺乳动物细胞中连续转录的人巨细胞病毒(CMV)启动子，以及用于增加转录后RNA的稳定性水平的牛生长激素多腺苷酸化信号序列。
表达融合蛋白的转化细胞
在本发明的又一方面，提供了已导入运载体的转化细胞。转化细胞的宿主细胞可以包括但不限于原核细胞、真核细胞和哺乳动物、植物、昆虫、真菌或细菌来源的细胞。作为原核细胞的例子，可以使用大肠杆菌。此外，作为真核细胞的例子，可以使用酵母。此外，对于哺乳动物细胞，可以使用CHO细胞、F2N细胞、CSO细胞、BHK细胞、Bowes黑色素瘤细胞、HeLa细胞、911细胞、AT1080细胞、A549细胞、HEK293细胞、HEK293T细胞等。然而，哺乳动物细胞不限于此，可以使用本领域技术人员已知可用作哺乳动物宿主细胞的任何细胞。
此外，为了将表达运载体导入宿主细胞，可以使用CaCl
如上所述，为了优化融合蛋白作为治疗剂的性质或为了任何其他目的，可以通过本领域技术人员已知的方法通过操纵宿主细胞所具有的糖基化相关基因来调节融合蛋白的糖基化模式(例如，唾液酸、岩藻糖基化、糖基化)。
产生融合蛋白的方法
在本发明的又一个方面中，提供了一种产生包含IL-2蛋白和CD80蛋白片段或其变体的融合蛋白的方法，该方法包括培养转化细胞。具体地，该生产方法可以包括：i)培养转化细胞以获得培养物；和ii)从培养物中收集融合蛋白。
可以使用本领域熟知的方法培养转化细胞。具体地，培养可以分批进行，也可以在分批补料或重复分批补料中连续进行。
融合蛋白或其二聚体的用途
在本发明的又一方面，提供了一种用于治疗或预防癌症或传染病的药物组合物，该组合物包含融合蛋白或两个融合蛋白连接在一起的融合蛋白二聚体作为活性成分，该融合蛋白包含IL-2蛋白和CD80蛋白片段或其变体。
包含IL-2蛋白和CD80蛋白片段或其变体的融合蛋白，或两个融合蛋白连接在一起的融合蛋白二聚体如上所述。
癌症可以选自由以下组成的组：胃癌、肝癌、肺癌、结直肠癌、乳腺癌、前列腺癌、卵巢癌、胰腺癌、宫颈癌、甲状腺癌、喉癌、急性髓性白血病、脑肿瘤、成神经细胞瘤、视网膜母细胞瘤、头颈癌、唾液腺癌和淋巴瘤。此外，传染病可以为选自由以下组成的组中的任一种：乙型肝炎、丙型肝炎、人乳头瘤病毒(HPV)感染、巨细胞病毒感染、病毒性呼吸道疾病、以及流行性感冒。
药物组合物的首选剂量因患者的病情和体重、疾病的严重程度、药物形式、施用途径和施用持续时间而异，并且可以由技术人员适当地选择。在本发明的用于治疗或预防癌症或传染病的药物组合物中，可以根据用途、剂型、混合目的等以任何量(有效量)包含活性成分，只要活性成分可以表现出抗癌活性或对传染病的治疗作用。基于组合物的总重量，其常规有效量将在按重量计0.001wt％至20.0wt％的范围内确定。在这里，术语“有效量”是指活性成分能够诱导抗癌作用或传染病治疗作用的量。这样的有效量可以在本领域技术人员的常识范围内通过实验确定。
如本文所用，术语“治疗”可用于表示治疗性治疗和预防性治疗。在这里，预防可用于表示个体的病理状况或疾病得到缓解或减轻。在实施方式中，术语“治疗”包括用于治疗包括人在内的哺乳动物的疾病的应用和任何形式的施用。此外，该术语包括：抑制或减缓疾病或疾病进展；并且包括恢复或修复受损或丧失的功能以使疾病部分或完全得到缓解；刺激低效的过程；或减轻严重疾病的含义。
如本文所用，术语“功效”是指可以由一个或多个参数确定的能力，例如，在诸如一年、五年或十年的特定时间段内的存活或无病存活。此外，参数可以包括对个体的至少一个肿瘤的大小的抑制。
生物利用度等药代动力学参数和清除率等潜在参数也可能影响功效。因此，“增强的功效”(例如，功效的改善)可能是由于增强的药代动力学参数和提高的功效，这可以通过比较试验动物或人类对象的清除率和肿瘤生长，或通过比较诸如生存率、复发率或无病生存率等参数来衡量。
如本文所用，术语“治疗有效量”或“药学有效量”是指有效预防或治疗所讨论疾病的化合物或组合物的量，该量足以以适用于医疗的合理的益处/风险比来治疗疾病，并且不会造成不良影响。有效量水平可以根据包括以下的因素来确定：患者的健康状况、疾病的类型和严重程度、药物的活性、患者对药物的敏感性、施用方式、施用时间、施用途径和排泄率、治疗持续时间、配方或同时使用的药物，以及医学领域众所周知的其他因素。在一个实施方式中，治疗有效量是指有效治疗癌症的药物量。
在这里，药物组合物可以进一步包含药学上可接受的载体。药学上可接受的载体可以是任何载体，只要该载体是适合递送给患者的无毒物质即可。可以含有蒸馏水、醇、脂肪、蜡和惰性固体作为载体。药学上可接受的佐剂(缓冲剂、分散剂)也可以包含在药物组合物中。
具体地，通过除了活性成分之外还包括药学上可接受的载体，可以使用本领域已知的常规方法根据其施用途径将药物组合物制备成肠胃外制剂。在这里，术语“药学上可接受的”是指载体不具有比要施用(开处方)的对象可以适应的更多的毒性，同时不抑制活性成分的活性。
当药物组合物制备成肠胃外制剂时，可以根据本领域已知的方法将其制成具有合适的载体的注射剂、透皮贴剂、鼻腔吸入剂或栓剂形式的制剂。在制成注射剂的情况下，可以使用无菌水、乙醇、多元醇(例如甘油或丙二醇)或其混合物作为合适的载体；并且可以优选使用等渗溶液，例如林格氏溶液、含有三乙醇胺的磷酸盐缓冲液(PBS)或注射用无菌水、5％葡萄糖等。药物组合物的配制是本领域已知的，具体可以参考雷明顿药物科学(第19版，1995年)等。该文件被认为是本说明书的一部分。
药物组合物的优选剂量可以在每天0.01μg/kg至10g/kg或0.01mg/kg至1g/kg的范围内，这取决于患者的状况、体重、性别、年龄、患者的严重程度和施用途径。该剂量可以每天施用一次或者可以分成每天数次。这样的剂量不应被解释为在任何方面限制本发明的范围。
可以施用(开处方)药物组合物的对象是哺乳动物和人类，特别优选人类。除活性成分外，本申请的药物组合物还可以含有任何已经过安全性验证且已知具有抗癌活性或对传染病具有治疗作用的化合物或天然提取物，以增强或加强抗癌活性。
在本发明的又一个方面，提供了包含IL-2蛋白和CD80蛋白片段或其变体的融合蛋白用于治疗癌症或传染病的用途。
在本发明的又一个方面，提供了包含IL-2蛋白和CD80蛋白片段或其变体的融合蛋白用于增强对癌症或传染病的治疗作用的用途。
在本发明的又一个方面，提供了包含IL-2蛋白和CD80蛋白片段或其变体的融合蛋白在制备用于治疗癌症或传染病的药物中的用途。
在本发明的又一个方面，提供了用于治疗癌症或传染病的方法，和/或用于增强对癌症或传染病的治疗作用的方法，该方法包括向对象施用包含IL-2蛋白和CD80蛋白片段或其变体的融合蛋白，或两个融合蛋白连接在一起的融合蛋白二聚体。
对象可以是患有癌症或传染病的个体。此外，对象可以是哺乳动物，优选人类。包含IL-2蛋白和CD80蛋白片段或其变体的融合蛋白，或两个融合蛋白连接在一起的融合蛋白二聚体如上所述。
融合蛋白或融合蛋白二聚体的施用途径、剂量和施用频率可以根据患者的状况和是否存在副作用而变化，因此可以按各种方式和量将融合蛋白或融合蛋白二聚体施用至对象。本领域技术人员可以在适当的范围内选择最佳的施用方法、剂量和施用频率。此外，融合蛋白或融合蛋白二聚体可以与就要治疗的疾病而言治疗作用已知的其他药物或生理活性物质组合施用，或者可以与其他药物以组合制剂的形式配制。
由于IL-2活性，本发明实施方式中的融合蛋白可以活化免疫细胞，例如自然杀伤细胞。因此，该融合蛋白可以有效地用于癌症和传染病。具体地，鉴定了与野生型相比具有2至5个氨基酸取代的IL-2变体，特别是这样的IL-2变体：在2、3、4或5个位置处包含氨基酸取代，其中氨基酸取代选自在SEQ ID NO:10的氨基酸序列中由R38A、F42A、Y45A、E61R和L72G组成的组；并且对IL-2受体α链的结合能力低，因此表现出相对于常规的IL-2的药理副作用改进的特性。因此，当单独使用或以融合蛋白的形式使用这种IL-2变体时，可以降低血管(或毛细血管)渗漏综合征(VLS)的发生率，VLS是通常已知的IL-2的问题。
具体实施方式
下文将通过以下实施例更为详细地描述本发明。然而，以下实施例仅用于说明本发明，并且本发明的范围不受以下实施例的限制。
制备例1.制备hCD80变体-Fc-IL-2变体：GI-101_P1至GI-101_P35
制备例1.1.构建hCD80变体-Fc-IL-2变体表达运载体
为了产生包含人CD80变体、Fc结构域和IL-2变体的融合蛋白，通过ThermoFisherScientific的Invitrogen GeneArt基因合成服务合成了总共35个多核苷酸。具体地，多核苷酸包含编码融合蛋白的核苷酸序列，该融合蛋白从N端开始按顺序包含：信号肽、CD80蛋白片段、Ig铰链、Fc结构域、接头和具有两个氨基酸取代(R38A、F42A)的IL-2变体(2M)。将多核苷酸插入pcDNA3_4运载体中。
hCD80变体-Fc-IL-2变体(GI-101_P1至GI-101_P35)融合蛋白的构建总结于表1中。
[表1]
制备例1.2.纯化hCD80变体-Fc-IL-2变体
将上述制备例1.1中制备的运载体导入CHO细胞(Expi-CHO
制备例1.2.1.纯化GI-101_P1至GI-101_P31
使用含有BAKEROND
使用TSKgel G3000SWXL柱(TOSOH Bioscience)通过尺寸排阻色谱测量214nm波长处的吸光度，以获得高度浓缩的融合蛋白。将分离纯化的融合蛋白在还原(R)或非还原(NR)条件下进行SDS-PAGE，并通过考马斯蓝染色鉴定(图52至82)。此外，通过使用尺寸排阻色谱法的分析获得的结果示于图85至117中。
制备例1.2.2.纯化GI-101_P32至GI-101_P35
使用含有BAKEROND
然后，在50mM Tris，pH7.5(或50mM Tris，500mM精氨酸，pH7.5)的条件下进行洗脱。将0.5N NaOH置于收集管中，然后收集融合蛋白。使用TSKgel G3000SWXL柱(TOSOHBioscience)通过尺寸排阻色谱测量214nm波长处的吸光度，以获得高度浓缩的融合蛋白。这里，将分离纯化的融合蛋白在还原(R)或非还原(NR)条件下进行SDS-PAGE，并通过考马斯蓝染色鉴定(图83至86)。此外，通过使用尺寸排阻色谱法的分析获得的结果示于图118至121中。
制备例2.制备hCD80变体-Fc-IL-2变体(2M)：GI-101_P36至GI-101_P42
制备例2.1.构建hCD80变体-Fc-IL-2变体(2M)表达运载体
为了产生包含人CD80变体、Fc结构域和IL-2变体的融合蛋白，通过ThermoFisherScientific的Invitrogen GeneArt基因合成服务合成了总共6个多核苷酸。具体地，多核苷酸包含编码融合蛋白的核苷酸序列，该融合蛋白从N端开始按顺序包含：信号肽、CD80蛋白片段、Ig铰链、Fc结构域、接头和具有两个氨基酸取代(R38A和F42A)的IL-2变体(2M)。将多核苷酸插入pcDNA3_4运载体中。
hCD80变体-Fc-IL-2变体(2M)(GI-101_P36至GI-101_P42)融合蛋白的构建总结于表2中。
[表2]
制备例2.2.纯化hCD80变体-Fc-IL-2变体(2M)
将上述制备例2.1中制备的运载体引入CHO细胞(Expi-CHO
使用含有BAKEROND
制备例3.制备hCD80变体-Fc-IL-2变体(3M)：GI-101_P43至GI-101_P49
制备例3.1.构建hCD80变体-Fc-IL-2变体(3M)表达运载体
为了产生包含人CD80变体、Fc结构域和IL-2变体的融合蛋白，通过ThermoFisherScientific的Invitrogen GeneArt基因合成服务合成了总共6个多核苷酸。具体地，多核苷酸包含编码融合蛋白的核苷酸序列，该融合蛋白从N端开始按顺序包含：信号肽、CD80蛋白片段、Ig铰链、Fc结构域、接头和具有三个氨基酸取代(R38A、F42A和Y45A)的IL-2变体(3M)。将多核苷酸插入pcDNA3_4运载体中。
hCD80-Fc-IL-2变体(GI-101_P43至GI-101_P49)融合蛋白的构建总结于表3中。
[表3]
制备例3.2.纯化hCD80变体-Fc-IL-2变体(3M)
将上述制备例3.1中制备的运载体引入CHO细胞(Expi-CHO
使用含有BAKEROND
实验例1.鉴定hCTLA-4与GI-101_P1至GI-101_P35的结合亲和力
将Ni-NTA生物传感器(带镍的Tris-NTA，ForteBio，18-5101)预先在96孔微孔板(GreinerBio-one，Cat:655209)中用200μl的1X Ni-NTA动力学缓冲液(10X动力学缓冲液，ForteBio，18-1042)水合。用1X Ni-NTA动力学缓冲液将要与生物传感器连接的配体(CTLA-4蛋白，人CTLA-4/CD152，His-Tag，Acro，CT4-H5229)稀释至浓度为1μg/ml。将要与配体连接的融合蛋白(GI-101_P1至GI-101_P35)用1X动力学缓冲液稀释至浓度为100nM。将80μl的各试剂置于384孔微孔板(GreinerBio-one，Cat：781209)中，并设置程序。
结果，测量了hCTLA-4与GI-101_P1至GI-101_P35之间的结合亲和力，分别如图120至156所示。
实验例2.鉴定hIL-2β受体与GI-101_P1至GI-101_P35的结合亲和力
将Ni-NTA生物传感器(带镍的Tris-NTA，ForteBio，18-5101)预先在96孔微孔板(GreinerBio-one，Cat:655209)中用200μl的1X Ni-NTA动力学缓冲液(10X动力学缓冲液，ForteBio，18-1042)水合。用1X Ni-NTA动力学缓冲液将要与生物传感器连接的配体(人IL-2Rβ/CD122蛋白，His-Tag，Acro，CD2-H5221)稀释至浓度为2μg/ml。将要与配体连接的融合蛋白(GI-101_P1至GI-101_P35)用1X动力学缓冲液稀释至浓度为100nM。将80μl的各试剂置于384孔微孔板(GreinerBio-one，Cat：781209)中，并设置程序。
结果，测量了hIL-2β受体与GI-101_P1至GI-101_P35之间的结合亲和力，分别如图122至156所示。
实验例3.鉴定hCTLA-4与GI-101_P36至GI-101_P49的结合亲和力
将Ni-NTA生物传感器(带镍的Tris-NTA，ForteBio，18-5101)预先在96孔微孔板(GreinerBio-one，Cat:655209)中用200μl的1X Ni-NTA动力学缓冲液(10X动力学缓冲液，ForteBio，18-1042)水合。用1X Ni-NTA动力学缓冲液将要与生物传感器连接的配体(CTLA-4蛋白，人CTLA-4/CD152，His-Tag，Acro，CT4-H5229)稀释至浓度为1μg/ml。将要与配体连接的融合蛋白(GI-101_P36至GI-101_P47)用1X动力学缓冲液稀释至浓度为100nM。将80μl的各试剂置于384孔微孔板(GreinerBio-one，Cat：781209)中，并设置程序。
结果，测量了hCTLA-4与GI-101_P36至GI-101_P49之间的结合亲和力，分别如图158至170所示。
实验例4.鉴定hPD-L1与GI-101_P36至GI-101_P49的结合亲和力
将Ni-NTA生物传感器(带镍的Tris-NTA，ForteBio，18-5101)预先在96孔微孔板(GreinerBio-one，Cat:655209)中用200μl的1X Ni-NTA动力学缓冲液(10X动力学缓冲液，ForteBio，18-1042)水合。用1X Ni-NTA动力学缓冲液将要与生物传感器连接的配体(PD-L1蛋白，人PD-L1/B7-H1蛋白，His-Tag Acro，PD1-H5229)稀释至浓度为1μg/ml。将要与配体连接的融合蛋白(GI-101_P36至GI-101_P49)用1X动力学缓冲液稀释至浓度为100nM。将80μl的各试剂置于384孔微孔板(GreinerBio-one，Cat：781209)中，并设置程序。
结果，测量了hPD-L1与GI-101_P36至GI-101_P49之间的结合亲和力，分别如图158至170所示。
实验例5.鉴定hIL-2β受体与GI-101_P46至GI-101_P49的结合亲和力
将Ni-NTA生物传感器(带镍的Tris-NTA，ForteBio，18-5101)预先在96孔微孔板(GreinerBio-one，Cat:655209)中用200μl的1X Ni-NTA动力学缓冲液(10X动力学缓冲液，ForteBio，18-1042)水合。用1X Ni-NTA动力学缓冲液将要与生物传感器连接的配体(人IL-2Rβ/CD122蛋白，His-Tag，Acro，CD2-H5221)稀释至浓度为2μg/ml。将要与配体连接的融合蛋白(GI-101P1至GI-101P35)用1X动力学缓冲液稀释至浓度为100nM。将80μl的各试剂置于384孔微孔板(GreinerBio-one，Cat：781209)中，并设置程序。
结果，测量了hIL-2β受体与GI-101_P36至GI-101_P49之间的结合亲和力，分别如图158至170所示。
序列表
<110> GI医诺微新
<120> 包含IL-2蛋白和CD80蛋白片段或其变体的融合蛋白及其用途
<130> SPO21-012-PCT/GII
<150> KR 10-2020-0033232
<151> 2020-03-18
<150> KR 10-2020-0034031
<151> 2020-03-19
<160> 115
<170> KopatentIn 3.0
<210> 1
<211> 25
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 信号肽 (TPA)
<400> 1
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala
2025
<210> 2
<211> 208
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> hB7-1:35-242
<400> 2
Val Ile His Val Thr Lys Glu Val Lys Glu Val Ala Thr Leu Ser Cys
1 5 1015
Gly His Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg Ile Tyr Trp
202530
Gln Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn
354045
Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn
505560
Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr
65707580
Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His
859095
Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro Ser
100 105 110
Ile Ser Asp Phe Glu Ile Pro Thr Ser Asn Ile Arg Arg Ile Ile Cys
115 120 125
Ser Thr Ser Gly Gly Phe Pro Glu Pro His Leu Ser Trp Leu Glu Asn
130 135 140
Gly Glu Glu Leu Asn Ala Ile Asn Thr Thr Val Ser Gln Asp Pro Glu
145 150 155 160
Thr Glu Leu Tyr Ala Val Ser Ser Lys Leu Asp Phe Asn Met Thr Thr
165 170 175
Asn His Ser Phe Met Cys Leu Ile Lys Tyr Gly His Leu Arg Val Asn
180 185 190
Gln Thr Phe Asn Trp Asn Thr Thr Lys Gln Glu His Phe Pro Asp Asn
195 200 205
<210> 3
<211> 30
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 铰链
<400> 3
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
1 5 1015
Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro
202530
<210> 4
<211> 216
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 免疫球蛋白fc
<400> 4
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 1015
Pro Lys Asp Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
202530
Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr
354045
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
505560
Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65707580
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
859095
Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Leu Gly
210 215
<210> 5
<211> 5
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头
<400> 5
Gly Gly Gly Gly Ser
1 5
<210> 6
<211> 133
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> hIL-2M
<400> 6
Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His
1 5 1015
Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys
202530
Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys
354045
Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys
505560
Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu
65707580
Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu
859095
Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala
100 105 110
Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile
115 120 125
Ile Ser Thr Leu Thr
130
<210> 7
<211> 617
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 包含IL-2的变体和CD80的片段的融合蛋白
<400> 7
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Gly Ser Gly Gly Gly Gly Ser
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly
245 250 255
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
260 265 270
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg
275 280 285
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
290 295 300
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
305 310 315 320
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
325 330 335
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
340 345 350
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
355 360 365
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
370 375 380
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
385 390 395 400
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
405 410 415
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
420 425 430
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
435 440 445
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala
450 455 460
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly
465 470 475 480
Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu
485 490 495
Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile
500 505 510
Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe
515 520 525
Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu
530 535 540
Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys
545 550 555 560
Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile
565 570 575
Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala
580 585 590
Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe
595 600 605
Cys Gln Ser Ile Ile Ser Thr Leu Thr
610 615
<210> 8
<211> 1857
<212> DNA
<213> 人工序列（Artificial Sequence）
<220>
<223> 编码融合蛋白 (GI101)的核苷酸
<400> 8
atggatgcta tgctgagagg cctgtgttgc gtgctgctgc tgtgtggcgc tgtgttcgtg 60
tctccttctc acgctgtgat ccacgtgacc aaagaagtga aagaggtcgc cacactgtcc 120
tgcggccaca acgtttcagt ggaagaactg gcccagacca ggatctactg gcagaaagaa 180
aagaaaatgg tgctgaccat gatgtccggc gacatgaaca tctggcctga gtacaagaac 240
cggaccatct tcgacatcac caacaacctg tccatcgtga ttctggccct gaggccttct 300
gatgagggca cctatgagtg cgtggtgctg aagtacgaga aggacgcctt caagcgcgag 360
cacctggctg aagtgacact gtccgtgaag gccgactttc ccacaccttc catctccgac 420
ttcgagatcc ctacctccaa catccggcgg atcatctgtt ctacctctgg cggctttcct 480
gagcctcacc tgtcttggct ggaaaacggc gaggaactga acgccatcaa caccaccgtg 540
tctcaggacc ccgaaaccga gctgtacgct gtgtcctcca agctggactt caacatgacc 600
accaaccaca gcttcatgtg cctgattaag tacggccacc tgagagtgaa ccagaccttc 660
aactggaaca ccaccaagca agagcacttc cctgacaatg gatctggcgg cggaggttct 720
ggcggaggtg gaagcggagg cggaggatct gctgagtcta agtatggccc tccttgtcct 780
ccatgtcctg ctccagaagc tgctggcgga ccctctgtgt tcctgtttcc tccaaagcct 840
aaggaccagc tcatgatctc tcggacaccc gaagtgacct gcgtggtggt ggatgtgtct 900
caagaggacc ctgaggtgca gttcaattgg tacgtggacg gcgtggaagt gcacaacgcc 960
aagaccaagc ctagagagga acagttcaac tccacctaca gagtggtgtc cgtgctgacc 1020
gtgctgcacc aggattggct gaacggcaaa gagtacaagt gcaaggtgtc caacaagggc 1080
ctgccttcca gcatcgaaaa gaccatctcc aaggctaagg gccagcctag ggaaccccag 1140
gtttacaccc tgcctccaag ccaagaggaa atgaccaaga accaggtgtc cctgacctgc 1200
ctggtcaagg gcttctaccc ttccgacatt gccgtggaat gggagtccaa tggccagcct 1260
gagaacaact acaagaccac acctcctgtg ctggactccg acggctcctt ctttctgtac 1320
tctcgcctga ccgtggacaa gtctagatgg caagagggca acgtgttctc ctgctctgtg 1380
ctgcacgagg ccctgcacaa tcactacacc cagaagtccc tgtctctgtc tcttggaggt 1440
ggtggcggtt ctgcccctac cagctcctct accaagaaaa cccagctcca gttggagcat 1500
ctgctgctgg acctccagat gattctgaac gggatcaaca actataagaa ccccaagctg 1560
accgccatgc tgaccgctaa gttctacatg cccaagaagg ccaccgagct gaagcacctc 1620
cagtgcctgg aagaagaact gaagcccctg gaagaggtgc tgaatctggc ccagtccaag 1680
aacttccacc tgaggccacg ggacctgatc agcaacatca acgtgatcgt gctggaactg 1740
aagggctccg agacaacctt tatgtgcgag tacgccgacg agacagccac catcgtggaa 1800
tttctgaacc ggtggatcac cttctgccag agcatcatct ccacactgac ctgatga 1857
<210> 9
<211> 592
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 融合蛋白(GI101)
<400> 9
Val Ile His Val Thr Lys Glu Val Lys Glu Val Ala Thr Leu Ser Cys
1 5 1015
Gly His Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg Ile Tyr Trp
202530
Gln Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn
354045
Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn
505560
Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr
65707580
Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His
859095
Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro Ser
100 105 110
Ile Ser Asp Phe Glu Ile Pro Thr Ser Asn Ile Arg Arg Ile Ile Cys
115 120 125
Ser Thr Ser Gly Gly Phe Pro Glu Pro His Leu Ser Trp Leu Glu Asn
130 135 140
Gly Glu Glu Leu Asn Ala Ile Asn Thr Thr Val Ser Gln Asp Pro Glu
145 150 155 160
Thr Glu Leu Tyr Ala Val Ser Ser Lys Leu Asp Phe Asn Met Thr Thr
165 170 175
Asn His Ser Phe Met Cys Leu Ile Lys Tyr Gly His Leu Arg Val Asn
180 185 190
Gln Thr Phe Asn Trp Asn Thr Thr Lys Gln Glu His Phe Pro Asp Asn
195 200 205
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
210 215 220
Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
225 230 235 240
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
245 250 255
Asp Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
260 265 270
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
275 280 285
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
290 295 300
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
305 310 315 320
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
325 330 335
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
340 345 350
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
355 360 365
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
370 375 380
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
385 390 395 400
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
405 410 415
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
420 425 430
Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
435 440 445
Leu Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser
450 455 460
Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu
465 470 475 480
Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr
485 490 495
Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu
500 505 510
Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val
515 520 525
Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu
530 535 540
Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr
545 550 555 560
Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe
565 570 575
Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
580 585 590
<210> 10
<211> 133
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> hIL-2
<400> 10
Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His
1 5 1015
Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys
202530
Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys
354045
Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys
505560
Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu
65707580
Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu
859095
Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala
100 105 110
Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile
115 120 125
Ile Ser Thr Leu Thr
130
<210> 11
<211> 288
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80
<400> 11
Met Gly His Thr Arg Arg Gln Gly Thr Ser Pro Ser Lys Cys Pro Tyr
1 5 1015
Leu Asn Phe Phe Gln Leu Leu Val Leu Ala Gly Leu Ser His Phe Cys
202530
Ser Gly Val Ile His Val Thr Lys Glu Val Lys Glu Val Ala Thr Leu
354045
Ser Cys Gly His Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg Ile
505560
Tyr Trp Gln Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp
65707580
Met Asn Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr
859095
Asn Asn Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly
100 105 110
Thr Tyr Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg
115 120 125
Glu His Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr
130 135 140
Pro Ser Ile Ser Asp Phe Glu Ile Pro Thr Ser Asn Ile Arg Arg Ile
145 150 155 160
Ile Cys Ser Thr Ser Gly Gly Phe Pro Glu Pro His Leu Ser Trp Leu
165 170 175
Glu Asn Gly Glu Glu Leu Asn Ala Ile Asn Thr Thr Val Ser Gln Asp
180 185 190
Pro Glu Thr Glu Leu Tyr Ala Val Ser Ser Lys Leu Asp Phe Asn Met
195 200 205
Thr Thr Asn His Ser Phe Met Cys Leu Ile Lys Tyr Gly His Leu Arg
210 215 220
Val Asn Gln Thr Phe Asn Trp Asn Thr Thr Lys Gln Glu His Phe Pro
225 230 235 240
Asp Asn Leu Leu Pro Ser Trp Ala Ile Thr Leu Ile Ser Val Asn Gly
245 250 255
Ile Phe Val Ile Cys Cys Leu Thr Tyr Cys Phe Ala Pro Arg Cys Arg
260 265 270
Glu Arg Arg Arg Asn Glu Arg Leu Arg Arg Glu Ser Val Arg Pro Val
275 280 285
<210> 12
<211> 215
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 修改的Fc
<400> 12
Ser His Thr Gln Pro Leu Gly Val Phe Leu Phe Pro Pro Lys Pro Lys
1 5 1015
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
202530
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
354045
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
505560
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
65707580
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
859095
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
100 105 110
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
115 120 125
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
130 135 140
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
145 150 155 160
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
165 170 175
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
180 185 190
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
195 200 205
Leu Ser Leu Ser Leu Gly Lys
210 215
<210> 13
<211> 306
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> mCD80
<400> 13
Met Ala Cys Asn Cys Gln Leu Met Gln Asp Thr Pro Leu Leu Lys Phe
1 5 1015
Pro Cys Pro Arg Leu Ile Leu Leu Phe Val Leu Leu Ile Arg Leu Ser
202530
Gln Val Ser Ser Asp Val Asp Glu Gln Leu Ser Lys Ser Val Lys Asp
354045
Lys Val Leu Leu Pro Cys Arg Tyr Asn Ser Pro His Glu Asp Glu Ser
505560
Glu Asp Arg Ile Tyr Trp Gln Lys His Asp Lys Val Val Leu Ser Val
65707580
Ile Ala Gly Lys Leu Lys Val Trp Pro Glu Tyr Lys Asn Arg Thr Leu
859095
Tyr Asp Asn Thr Thr Tyr Ser Leu Ile Ile Leu Gly Leu Val Leu Ser
100 105 110
Asp Arg Gly Thr Tyr Ser Cys Val Val Gln Lys Lys Glu Arg Gly Thr
115 120 125
Tyr Glu Val Lys His Leu Ala Leu Val Lys Leu Ser Ile Lys Ala Asp
130 135 140
Phe Ser Thr Pro Asn Ile Thr Glu Ser Gly Asn Pro Ser Ala Asp Thr
145 150 155 160
Lys Arg Ile Thr Cys Phe Ala Ser Gly Gly Phe Pro Lys Pro Arg Phe
165 170 175
Ser Trp Leu Glu Asn Gly Arg Glu Leu Pro Gly Ile Asn Thr Thr Ile
180 185 190
Ser Gln Asp Pro Glu Ser Glu Leu Tyr Thr Ile Ser Ser Gln Leu Asp
195 200 205
Phe Asn Thr Thr Arg Asn His Thr Ile Lys Cys Leu Ile Lys Tyr Gly
210 215 220
Asp Ala His Val Ser Glu Asp Phe Thr Trp Glu Lys Pro Pro Glu Asp
225 230 235 240
Pro Pro Asp Ser Lys Asn Thr Leu Val Leu Phe Gly Ala Gly Phe Gly
245 250 255
Ala Val Ile Thr Val Val Val Ile Val Val Ile Ile Lys Cys Phe Cys
260 265 270
Lys His Arg Ser Cys Phe Arg Arg Asn Glu Ala Ser Arg Glu Thr Asn
275 280 285
Asn Ser Leu Thr Phe Gly Pro Glu Glu Ala Leu Ala Glu Gln Thr Val
290 295 300
Phe Leu
305
<210> 14
<211> 1848
<212> DNA
<213> 人工序列（Artificial Sequence）
<220>
<223> 编码融合蛋白(mGI101)的核苷酸
<400> 14
atggatgcta tgctgagagg cctgtgttgc gtgctgctgc tgtgtggcgc tgtgttcgtg 60
tctccttctc acgctgtgga cgagcagctc tccaagtccg tgaaggataa ggtcctgctg 120
ccttgccggt acaactctcc tcacgaggac gagtctgagg accggatcta ctggcagaaa 180
cacgacaagg tggtgctgtc cgtgatcgcc ggaaagctga aagtgtggcc tgagtacaag 240
aacaggaccc tgtacgacaa caccacctac agcctgatca tcctgggcct cgtgctgagc 300
gatagaggca cctattcttg cgtggtgcag aagaaagagc ggggcaccta cgaagtgaag 360
cacctggctc tggtcaagct gtccatcaag gccgacttca gcacccctaa catcaccgag 420
tctggcaacc cttccgccga caccaagaga atcacctgtt tcgcctctgg cggcttccct 480
aagcctcggt tctcttggct ggaaaacggc agagagctgc ccggcatcaa taccaccatt 540
tctcaggacc cagagtccga gctgtacacc atctccagcc agctcgactt taacaccacc 600
agaaaccaca ccatcaagtg cctgattaag tacggcgacg cccacgtgtc cgaggacttt 660
acttgggaga aacctcctga ggaccctcct gactctggat ctggcggcgg aggttctggc 720
ggaggtggaa gcggaggcgg aggatctgct gagtctaagt atggccctcc ttgtcctcca 780
tgtcctgctc cagaagctgc tggcggaccc tctgtgttcc tgtttcctcc aaagcctaag 840
gaccagctca tgatctctcg gacccctgaa gtgacctgcg tggtggtgga tgtgtctcaa 900
gaggaccctg aggtgcagtt caattggtac gtggacggcg tggaagtgca caacgccaag 960
accaagccta gagaggaaca gttcaactcc acctatagag tggtgtccgt gctgaccgtg 1020
ctgcaccagg attggctgaa cggcaaagag tacaagtgca aggtgtccaa caagggcctg 1080
ccttccagca tcgaaaagac catcagcaag gctaagggcc agcctaggga accccaggtt 1140
tacaccctgc ctccaagcca agaggaaatg accaagaacc aggtgtccct gacctgcctg 1200
gtcaagggct tctacccttc cgacattgcc gtggaatggg agtccaatgg ccagcctgag 1260
aacaactaca agaccacacc tcctgtgctg gactccgacg gctccttctt tctgtactct 1320
cgcctgaccg tggacaagtc taggtggcaa gagggcaacg tgttctcctg ctctgtgctg 1380
cacgaggctc tgcacaacca ctacacccag aagtccctgt ctctgtctct tggaggtggt 1440
ggcggttctg cccctacctc cagctctacc aagaaaaccc agctccagtt ggagcatctg 1500
ctgctggacc tccagatgat cctgaatggc atcaacaatt acaagaaccc caagctgacc 1560
gccatgctga ccgctaagtt ctacatgccc aagaaggcca ccgagctgaa gcacttgcag 1620
tgcctggaag aggaactgaa gcccctggaa gaagtgctga atctggccca gtccaagaac 1680
ttccacctga ggcctaggga cctgatctcc aacatcaacg tgatcgtgct ggaactgaaa 1740
ggctccgaga caaccttcat gtgcgagtac gccgacgaga cagccaccat cgtggaattt 1800
ctgaaccggt ggatcacctt ctgccagagc atcatctcca cactgacc 1848
<210> 15
<211> 616
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 融合蛋白 (mGI101)
<400> 15
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Asp Glu Gln Leu Ser Lys
202530
Ser Val Lys Asp Lys Val Leu Leu Pro Cys Arg Tyr Asn Ser Pro His
354045
Glu Asp Glu Ser Glu Asp Arg Ile Tyr Trp Gln Lys His Asp Lys Val
505560
Val Leu Ser Val Ile Ala Gly Lys Leu Lys Val Trp Pro Glu Tyr Lys
65707580
Asn Arg Thr Leu Tyr Asp Asn Thr Thr Tyr Ser Leu Ile Ile Leu Gly
859095
Leu Val Leu Ser Asp Arg Gly Thr Tyr Ser Cys Val Val Gln Lys Lys
100 105 110
Glu Arg Gly Thr Tyr Glu Val Lys His Leu Ala Leu Val Lys Leu Ser
115 120 125
Ile Lys Ala Asp Phe Ser Thr Pro Asn Ile Thr Glu Ser Gly Asn Pro
130 135 140
Ser Ala Asp Thr Lys Arg Ile Thr Cys Phe Ala Ser Gly Gly Phe Pro
145 150 155 160
Lys Pro Arg Phe Ser Trp Leu Glu Asn Gly Arg Glu Leu Pro Gly Ile
165 170 175
Asn Thr Thr Ile Ser Gln Asp Pro Glu Ser Glu Leu Tyr Thr Ile Ser
180 185 190
Ser Gln Leu Asp Phe Asn Thr Thr Arg Asn His Thr Ile Lys Cys Leu
195 200 205
Ile Lys Tyr Gly Asp Ala His Val Ser Glu Asp Phe Thr Trp Glu Lys
210 215 220
Pro Pro Glu Asp Pro Pro Asp Ser Gly Ser Gly Gly Gly Gly Ser Gly
225 230 235 240
Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro
245 250 255
Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val
260 265 270
Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg Thr
275 280 285
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
290 295 300
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
305 310 315 320
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
325 330 335
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
340 345 350
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
355 360 365
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
370 375 380
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
385 390 395 400
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
405 410 415
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
420 425 430
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
435 440 445
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala Leu
450 455 460
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly
465 470 475 480
Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln
485 490 495
Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn
500 505 510
Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr
515 520 525
Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu
530 535 540
Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn
545 550 555 560
Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val
565 570 575
Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp
580 585 590
Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys
595 600 605
Gln Ser Ile Ile Ser Thr Leu Thr
610 615
<210> 16
<211> 1437
<212> DNA
<213> 人工序列（Artificial Sequence）
<220>
<223> 编码融合蛋白(GI101C1)的核苷酸
<400> 16
atggatgcta tgctgagagg cctgtgttgc gtgctgctgc tgtgtggcgc tgtgttcgtg 60
tctccttctc acgctgtgat ccacgtgacc aaagaagtga aagaggtcgc cacactgtcc 120
tgcggccaca acgtttcagt ggaagaactg gcccagacca ggatctactg gcagaaagaa 180
aagaaaatgg tgctgaccat gatgtccggc gacatgaaca tctggcctga gtacaagaac 240
cggaccatct tcgacatcac caacaacctg tccatcgtga ttctggccct gaggccttct 300
gatgagggca cctatgagtg cgtggtgctg aagtacgaga aggacgcctt caagcgcgag 360
cacctggctg aagtgacact gtccgtgaag gccgactttc ccacaccttc catctccgac 420
ttcgagatcc ctacctccaa catccggcgg atcatctgtt ctacctctgg cggctttcct 480
gagcctcacc tgtcttggct ggaaaacggc gaggaactga acgccatcaa caccaccgtg 540
tctcaggacc ccgaaaccga gctgtacgct gtgtcctcca agctggactt caacatgacc 600
accaaccaca gcttcatgtg cctgattaag tacggccacc tgagagtgaa ccagaccttc 660
aactggaaca ccaccaagca agagcacttc cctgacaatg gatctggcgg cggaggttct 720
ggcggaggtg gaagcggagg cggaggatct gctgagtcta agtatggccc tccttgtcct 780
ccatgtcctg ctccagaagc tgctggcgga ccctctgtgt tcctgtttcc tccaaagcct 840
aaggaccagc tcatgatctc tcggacaccc gaagtgacct gcgtggtggt ggatgtgtct 900
caagaggacc ctgaggtgca gttcaattgg tacgtggacg gcgtggaagt gcacaacgcc 960
aagaccaagc ctagagagga acagttcaac tccacctaca gagtggtgtc cgtgctgacc 1020
gtgctgcacc aggattggct gaacggcaaa gagtacaagt gcaaggtgtc caacaagggc 1080
ctgccttcca gcatcgaaaa gaccatctcc aaggctaagg gccagcctag ggaaccccag 1140
gtttacaccc tgcctccaag ccaagaggaa atgaccaaga accaggtgtc cctgacctgc 1200
ctggtcaagg gcttctaccc ttccgacatt gccgtggaat gggagtccaa tggccagcct 1260
gagaacaact acaagaccac acctcctgtg ctggactccg acggctcctt ctttctgtac 1320
tctcgcctga ccgtggacaa gtctaggtgg caagagggca acgtgttctc ctgctctgtg 1380
ctgcacgagg ccctgcacaa tcactacacc cagaagtccc tgtctctgtc cctgggc 1437
<210> 17
<211> 454
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 融合蛋白 (GI101C1)
<400> 17
Val Ile His Val Thr Lys Glu Val Lys Glu Val Ala Thr Leu Ser Cys
1 5 1015
Gly His Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg Ile Tyr Trp
202530
Gln Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn
354045
Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn
505560
Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr
65707580
Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His
859095
Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro Ser
100 105 110
Ile Ser Asp Phe Glu Ile Pro Thr Ser Asn Ile Arg Arg Ile Ile Cys
115 120 125
Ser Thr Ser Gly Gly Phe Pro Glu Pro His Leu Ser Trp Leu Glu Asn
130 135 140
Gly Glu Glu Leu Asn Ala Ile Asn Thr Thr Val Ser Gln Asp Pro Glu
145 150 155 160
Thr Glu Leu Tyr Ala Val Ser Ser Lys Leu Asp Phe Asn Met Thr Thr
165 170 175
Asn His Ser Phe Met Cys Leu Ile Lys Tyr Gly His Leu Arg Val Asn
180 185 190
Gln Thr Phe Asn Trp Asn Thr Thr Lys Gln Glu His Phe Pro Asp Asn
195 200 205
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
210 215 220
Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
225 230 235 240
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
245 250 255
Asp Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
260 265 270
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
275 280 285
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
290 295 300
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
305 310 315 320
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
325 330 335
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
340 345 350
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
355 360 365
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
370 375 380
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
385 390 395 400
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
405 410 415
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
420 425 430
Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
435 440 445
Leu Ser Leu Ser Leu Gly
450
<210> 18
<211> 1176
<212> DNA
<213> 人工序列（Artificial Sequence）
<220>
<223> 编码融合蛋白(GI101C2)的核苷酸
<400> 18
atggatgcta tgctgagagg cctgtgttgc gtgctgctgc tgtgtggcgc tgtgttcgtg 60
tctccatctc acgccgctga gtctaagtac ggccctcctt gtcctccatg tcctgctcca 120
gaagctgctg gcggaccctc tgtgttcctg tttcctccaa agcctaagga ccagctcatg 180
atctctcgga cccctgaagt gacctgcgtg gtggtggatg tgtctcaaga ggaccctgag 240
gtgcagttca attggtacgt ggacggcgtg gaagtgcaca acgccaagac caagcctaga 300
gaggaacagt tcaactccac ctacagagtg gtgtccgtgc tgaccgtgct gcaccaggat 360
tggctgaacg gcaaagagta caagtgcaag gtgtccaaca agggcctgcc ttccagcatc 420
gaaaagacca tctccaaggc taagggccag cctagggaac cccaggttta caccctgcct 480
ccaagccaag aggaaatgac caagaaccag gtgtccctga cctgcctggt caagggcttc 540
tacccttccg acattgccgt ggaatgggag tccaatggcc agcctgagaa caactacaag 600
accacacctc ctgtgctgga ctccgacggc tccttctttc tgtactctcg cctgaccgtg 660
gacaagtcta ggtggcaaga gggcaacgtg ttctcctgct ctgtgctgca cgaggccctg 720
cacaatcact acacccagaa gtccctgtct ctgtctcttg gcggaggcgg aggatctgct 780
cctacctcca gctccaccaa gaaaacccag ctccagttgg agcatctgct gctggacctc 840
cagatgatcc tgaatggcat caacaattac aagaacccca agctgaccgc catgctgacc 900
gctaagttct acatgcccaa gaaggccacc gagctgaagc acctccagtg cctggaagag 960
gaactgaagc ccctggaaga agtgctgaat ctggcccagt ccaagaactt ccacctgagg 1020
cctagggacc tgatctccaa catcaacgtg atcgtgctgg aactgaaagg ctccgagaca 1080
accttcatgt gcgagtacgc cgacgagaca gccaccatcg tggaatttct gaaccggtgg 1140
atcaccttct gccagtccat catctccaca ctgacc 1176
<210> 19
<211> 367
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 融合蛋白 (GI101C2)
<400> 19
Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu
1 5 1015
Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
202530
Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
354045
Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly
505560
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn
65707580
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
859095
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro
100 105 110
Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
115 120 125
Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn
130 135 140
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
145 150 155 160
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
165 170 175
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg
180 185 190
Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys
195 200 205
Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
210 215 220
Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser
225 230 235 240
Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln
245 250 255
Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala
260 265 270
Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys
275 280 285
His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu
290 295 300
Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile
305 310 315 320
Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr
325 330 335
Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu
340 345 350
Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
355 360 365
<210> 20
<211> 1434
<212> DNA
<213> 人工序列（Artificial Sequence）
<220>
<223> 编码融合蛋白(mGI101C1)的核苷酸
<400> 20
atggatgcta tgctgagagg cctgtgttgc gtgctgctgc tgtgtggcgc tgtgttcgtg 60
tctccttctc acgctgtgga cgagcagctc tccaagtccg tgaaggataa ggtcctgctg 120
ccttgccggt acaactctcc tcacgaggac gagtctgagg accggatcta ctggcagaaa 180
cacgacaagg tggtgctgtc cgtgatcgcc ggaaagctga aagtgtggcc tgagtacaag 240
aacaggaccc tgtacgacaa caccacctac agcctgatca tcctgggcct cgtgctgagc 300
gatagaggca cctattcttg cgtggtgcag aagaaagagc ggggcaccta cgaagtgaag 360
cacctggctc tggtcaagct gtccatcaag gccgacttca gcacccctaa catcaccgag 420
tctggcaacc cttccgccga caccaagaga atcacctgtt tcgcctctgg cggcttccct 480
aagcctcggt tctcttggct ggaaaacggc agagagctgc ccggcatcaa taccaccatt 540
tctcaggacc cagagtccga gctgtacacc atctccagcc agctcgactt taacaccacc 600
agaaaccaca ccatcaagtg cctgattaag tacggcgacg cccacgtgtc cgaggacttt 660
acttgggaga aacctcctga ggaccctcct gactctggat ctggcggcgg aggttctggc 720
ggaggtggaa gcggaggcgg aggatctgct gagtctaagt atggccctcc ttgtcctcca 780
tgtcctgctc cagaagctgc tggcggaccc tctgtgttcc tgtttcctcc aaagcctaag 840
gaccagctca tgatctctcg gacccctgaa gtgacctgcg tggtggtgga tgtgtctcaa 900
gaggaccctg aggtgcagtt caattggtac gtggacggcg tggaagtgca caacgccaag 960
accaagccta gagaggaaca gttcaactcc acctatagag tggtgtccgt gctgaccgtg 1020
ctgcaccagg attggctgaa cggcaaagag tacaagtgca aggtgtccaa caagggcctg 1080
ccttccagca tcgaaaagac catcagcaag gctaagggcc agcctaggga accccaggtt 1140
tacaccctgc ctccaagcca agaggaaatg accaagaacc aggtgtccct gacctgcctg 1200
gtcaagggct tctacccttc cgacattgcc gtggaatggg agtccaatgg ccagcctgag 1260
aacaactaca agaccacacc tcctgtgctg gactccgacg gctccttctt tctgtactct 1320
cgcctgaccg tggacaagtc taggtggcaa gagggcaacg tgttctcctg ctctgtgctg 1380
cacgaggctc tgcacaacca ctacacccag aagtccctgt ctctgtccct gggc 1434
<210> 21
<211> 478
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 融合蛋白 (mGI101C1)
<400> 21
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Asp Glu Gln Leu Ser Lys
202530
Ser Val Lys Asp Lys Val Leu Leu Pro Cys Arg Tyr Asn Ser Pro His
354045
Glu Asp Glu Ser Glu Asp Arg Ile Tyr Trp Gln Lys His Asp Lys Val
505560
Val Leu Ser Val Ile Ala Gly Lys Leu Lys Val Trp Pro Glu Tyr Lys
65707580
Asn Arg Thr Leu Tyr Asp Asn Thr Thr Tyr Ser Leu Ile Ile Leu Gly
859095
Leu Val Leu Ser Asp Arg Gly Thr Tyr Ser Cys Val Val Gln Lys Lys
100 105 110
Glu Arg Gly Thr Tyr Glu Val Lys His Leu Ala Leu Val Lys Leu Ser
115 120 125
Ile Lys Ala Asp Phe Ser Thr Pro Asn Ile Thr Glu Ser Gly Asn Pro
130 135 140
Ser Ala Asp Thr Lys Arg Ile Thr Cys Phe Ala Ser Gly Gly Phe Pro
145 150 155 160
Lys Pro Arg Phe Ser Trp Leu Glu Asn Gly Arg Glu Leu Pro Gly Ile
165 170 175
Asn Thr Thr Ile Ser Gln Asp Pro Glu Ser Glu Leu Tyr Thr Ile Ser
180 185 190
Ser Gln Leu Asp Phe Asn Thr Thr Arg Asn His Thr Ile Lys Cys Leu
195 200 205
Ile Lys Tyr Gly Asp Ala His Val Ser Glu Asp Phe Thr Trp Glu Lys
210 215 220
Pro Pro Glu Asp Pro Pro Asp Ser Gly Ser Gly Gly Gly Gly Ser Gly
225 230 235 240
Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro
245 250 255
Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val
260 265 270
Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg Thr
275 280 285
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
290 295 300
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
305 310 315 320
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
325 330 335
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
340 345 350
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
355 360 365
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
370 375 380
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
385 390 395 400
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
405 410 415
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
420 425 430
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
435 440 445
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala Leu
450 455 460
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
465 470 475
<210> 22
<211> 133
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> IL-2的变体 (3M, M45)
<400> 22
Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His
1 5 1015
Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys
202530
Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Ala Met Pro Lys
354045
Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys
505560
Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu
65707580
Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu
859095
Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala
100 105 110
Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile
115 120 125
Ile Ser Thr Leu Thr
130
<210> 23
<211> 133
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> IL-2的变体 (3M, M61)
<400> 23
Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His
1 5 1015
Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys
202530
Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys
354045
Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Arg Glu Leu Lys
505560
Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu
65707580
Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu
859095
Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala
100 105 110
Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile
115 120 125
Ile Ser Thr Leu Thr
130
<210> 24
<211> 133
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> IL-2的变体 (3M, M72)
<400> 24
Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His
1 5 1015
Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys
202530
Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys
354045
Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys
505560
Pro Leu Glu Glu Val Leu Asn Gly Ala Gln Ser Lys Asn Phe His Leu
65707580
Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu
859095
Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala
100 105 110
Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile
115 120 125
Ile Ser Thr Leu Thr
130
<210> 25
<211> 1851
<212> DNA
<213> 人工序列（Artificial Sequence）
<220>
<223> 编码融合蛋白(GI102-M45)的核苷酸
<400> 25
atggatgcta tgctgagagg cctgtgttgc gtgctgctgc tgtgtggcgc tgtgttcgtg 60
tctccttctc acgctgtgat ccacgtgacc aaagaagtga aagaggtcgc cacactgtcc 120
tgcggccaca acgtttcagt ggaagaactg gcccagacca ggatctactg gcagaaagaa 180
aagaaaatgg tgctgaccat gatgtccggc gacatgaaca tctggcctga gtacaagaac 240
cggaccatct tcgacatcac caacaacctg tccatcgtga ttctggccct gaggccttct 300
gatgagggca cctatgagtg cgtggtgctg aagtacgaga aggacgcctt caagcgcgag 360
cacctggctg aagtgacact gtccgtgaag gccgactttc ccacaccttc catctccgac 420
ttcgagatcc ctacctccaa catccggcgg atcatctgtt ctacctctgg cggctttcct 480
gagcctcacc tgtcttggct ggaaaacggc gaggaactga acgccatcaa caccaccgtg 540
tctcaggacc ccgaaaccga gctgtacgct gtgtcctcca agctggactt caacatgacc 600
accaaccaca gcttcatgtg cctgattaag tacggccacc tgagagtgaa ccagaccttc 660
aactggaaca ccaccaagca agagcacttc cctgacaatg gatctggcgg cggaggttct 720
ggcggaggtg gaagcggagg cggaggatct gctgagtcta agtatggccc tccttgtcct 780
ccatgtcctg ctccagaagc tgctggcgga ccctctgtgt tcctgtttcc tccaaagcct 840
aaggaccagc tcatgatctc tcggacaccc gaagtgacct gcgtggtggt ggatgtgtct 900
caagaggacc ctgaggtgca gttcaattgg tacgtggacg gcgtggaagt gcacaacgcc 960
aagaccaagc ctagagagga acagttcaac tccacctaca gagtggtgtc cgtgctgacc 1020
gtgctgcacc aggattggct gaacggcaaa gagtacaagt gcaaggtgtc caacaagggc 1080
ctgccttcca gcatcgaaaa gaccatctcc aaggctaagg gccagcctag ggaaccccag 1140
gtttacaccc tgcctccaag ccaagaggaa atgaccaaga accaggtgtc cctgacctgc 1200
ctggtcaagg gcttctaccc ttccgacatt gccgtggaat gggagtccaa tggccagcct 1260
gagaacaact acaagaccac acctcctgtg ctggactccg acggctcctt ctttctgtac 1320
tctcgcctga ccgtggacaa gtctagatgg caagagggca acgtgttctc ctgctctgtg 1380
ctgcacgagg ccctgcacaa tcactacacc cagaagtccc tgtctctgtc tcttggaggt 1440
ggtggcggtt ctgcccctac cagctcctct accaagaaaa cccagctcca gttggagcat 1500
ctgctgctgg acctccagat gattctgaac gggatcaaca actataagaa ccccaagctg 1560
accgccatgc tgaccgctaa gttcgccatg cccaagaagg ccaccgagct gaagcacctc 1620
cagtgcctgg aagaagaact gaagcccctg gaagaggtgc tgaatctggc ccagtccaag 1680
aacttccacc tgaggccacg ggacctgatc agcaacatca acgtgatcgt gctggaactg 1740
aagggctccg agacaacctt tatgtgcgag tacgccgacg agacagccac catcgtggaa 1800
tttctgaacc ggtggatcac cttctgccag agcatcatct ccacactgac c 1851
<210> 26
<211> 592
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 融合蛋白 (GI102-M45)
<400> 26
Val Ile His Val Thr Lys Glu Val Lys Glu Val Ala Thr Leu Ser Cys
1 5 1015
Gly His Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg Ile Tyr Trp
202530
Gln Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn
354045
Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn
505560
Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr
65707580
Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His
859095
Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro Ser
100 105 110
Ile Ser Asp Phe Glu Ile Pro Thr Ser Asn Ile Arg Arg Ile Ile Cys
115 120 125
Ser Thr Ser Gly Gly Phe Pro Glu Pro His Leu Ser Trp Leu Glu Asn
130 135 140
Gly Glu Glu Leu Asn Ala Ile Asn Thr Thr Val Ser Gln Asp Pro Glu
145 150 155 160
Thr Glu Leu Tyr Ala Val Ser Ser Lys Leu Asp Phe Asn Met Thr Thr
165 170 175
Asn His Ser Phe Met Cys Leu Ile Lys Tyr Gly His Leu Arg Val Asn
180 185 190
Gln Thr Phe Asn Trp Asn Thr Thr Lys Gln Glu His Phe Pro Asp Asn
195 200 205
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
210 215 220
Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
225 230 235 240
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
245 250 255
Asp Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
260 265 270
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
275 280 285
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
290 295 300
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
305 310 315 320
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
325 330 335
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
340 345 350
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
355 360 365
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
370 375 380
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
385 390 395 400
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
405 410 415
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
420 425 430
Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
435 440 445
Leu Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser
450 455 460
Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu
465 470 475 480
Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr
485 490 495
Ala Met Leu Thr Ala Lys Phe Ala Met Pro Lys Lys Ala Thr Glu Leu
500 505 510
Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val
515 520 525
Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu
530 535 540
Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr
545 550 555 560
Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe
565 570 575
Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
580 585 590
<210> 27
<211> 1851
<212> DNA
<213> 人工序列（Artificial Sequence）
<220>
<223> 编码融合蛋白(GI102-M61)的核苷酸
<400> 27
atggatgcta tgctgagagg cctgtgttgc gtgctgctgc tgtgtggcgc tgtgttcgtg 60
tctccttctc acgctgtgat ccacgtgacc aaagaagtga aagaggtcgc cacactgtcc 120
tgcggccaca acgtttcagt ggaagaactg gcccagacca ggatctactg gcagaaagaa 180
aagaaaatgg tgctgaccat gatgtccggc gacatgaaca tctggcctga gtacaagaac 240
cggaccatct tcgacatcac caacaacctg tccatcgtga ttctggccct gaggccttct 300
gatgagggca cctatgagtg cgtggtgctg aagtacgaga aggacgcctt caagcgcgag 360
cacctggctg aagtgacact gtccgtgaag gccgactttc ccacaccttc catctccgac 420
ttcgagatcc ctacctccaa catccggcgg atcatctgtt ctacctctgg cggctttcct 480
gagcctcacc tgtcttggct ggaaaacggc gaggaactga acgccatcaa caccaccgtg 540
tctcaggacc ccgaaaccga gctgtacgct gtgtcctcca agctggactt caacatgacc 600
accaaccaca gcttcatgtg cctgattaag tacggccacc tgagagtgaa ccagaccttc 660
aactggaaca ccaccaagca agagcacttc cctgacaatg gatctggcgg cggaggttct 720
ggcggaggtg gaagcggagg cggaggatct gctgagtcta agtatggccc tccttgtcct 780
ccatgtcctg ctccagaagc tgctggcgga ccctctgtgt tcctgtttcc tccaaagcct 840
aaggaccagc tcatgatctc tcggacaccc gaagtgacct gcgtggtggt ggatgtgtct 900
caagaggacc ctgaggtgca gttcaattgg tacgtggacg gcgtggaagt gcacaacgcc 960
aagaccaagc ctagagagga acagttcaac tccacctaca gagtggtgtc cgtgctgacc 1020
gtgctgcacc aggattggct gaacggcaaa gagtacaagt gcaaggtgtc caacaagggc 1080
ctgccttcca gcatcgaaaa gaccatctcc aaggctaagg gccagcctag ggaaccccag 1140
gtttacaccc tgcctccaag ccaagaggaa atgaccaaga accaggtgtc cctgacctgc 1200
ctggtcaagg gcttctaccc ttccgacatt gccgtggaat gggagtccaa tggccagcct 1260
gagaacaact acaagaccac acctcctgtg ctggactccg acggctcctt ctttctgtac 1320
tctcgcctga ccgtggacaa gtctagatgg caagagggca acgtgttctc ctgctctgtg 1380
ctgcacgagg ccctgcacaa tcactacacc cagaagtccc tgtctctgtc tcttggaggt 1440
ggtggcggtt ctgcccctac cagctcctct accaagaaaa cccagctcca gttggagcat 1500
ctgctgctgg acctccagat gattctgaac gggatcaaca actataagaa ccccaagctg 1560
accgccatgc tgaccgctaa gttctacatg cccaagaagg ccaccgagct gaagcacctc 1620
cagtgcctgg aaagggaact gaagcccctg gaagaggtgc tgaatctggc ccagtccaag 1680
aacttccacc tgaggccacg ggacctgatc agcaacatca acgtgatcgt gctggaactg 1740
aagggctccg agacaacctt tatgtgcgag tacgccgacg agacagccac catcgtggaa 1800
tttctgaacc ggtggatcac cttctgccag agcatcatct ccacactgac c 1851
<210> 28
<211> 592
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 融合蛋白 (GI102-M61)
<400> 28
Val Ile His Val Thr Lys Glu Val Lys Glu Val Ala Thr Leu Ser Cys
1 5 1015
Gly His Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg Ile Tyr Trp
202530
Gln Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn
354045
Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn
505560
Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr
65707580
Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His
859095
Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro Ser
100 105 110
Ile Ser Asp Phe Glu Ile Pro Thr Ser Asn Ile Arg Arg Ile Ile Cys
115 120 125
Ser Thr Ser Gly Gly Phe Pro Glu Pro His Leu Ser Trp Leu Glu Asn
130 135 140
Gly Glu Glu Leu Asn Ala Ile Asn Thr Thr Val Ser Gln Asp Pro Glu
145 150 155 160
Thr Glu Leu Tyr Ala Val Ser Ser Lys Leu Asp Phe Asn Met Thr Thr
165 170 175
Asn His Ser Phe Met Cys Leu Ile Lys Tyr Gly His Leu Arg Val Asn
180 185 190
Gln Thr Phe Asn Trp Asn Thr Thr Lys Gln Glu His Phe Pro Asp Asn
195 200 205
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
210 215 220
Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
225 230 235 240
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
245 250 255
Asp Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
260 265 270
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
275 280 285
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
290 295 300
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
305 310 315 320
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
325 330 335
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
340 345 350
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
355 360 365
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
370 375 380
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
385 390 395 400
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
405 410 415
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
420 425 430
Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
435 440 445
Leu Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser
450 455 460
Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu
465 470 475 480
Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr
485 490 495
Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu
500 505 510
Lys His Leu Gln Cys Leu Glu Arg Glu Leu Lys Pro Leu Glu Glu Val
515 520 525
Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu
530 535 540
Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr
545 550 555 560
Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe
565 570 575
Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
580 585 590
<210> 29
<211> 1857
<212> DNA
<213> 人工序列（Artificial Sequence）
<220>
<223> 编码融合蛋白(GI102-M72)的核苷酸
<400> 29
atggatgcta tgctgagagg cctgtgttgc gtgctgctgc tgtgtggcgc tgtgttcgtg 60
tctccttctc acgctgtgat ccacgtgacc aaagaagtga aagaggtcgc cacactgtcc 120
tgcggccaca acgtttcagt ggaagaactg gcccagacca ggatctactg gcagaaagaa 180
aagaaaatgg tgctgaccat gatgtccggc gacatgaaca tctggcctga gtacaagaac 240
cggaccatct tcgacatcac caacaacctg tccatcgtga ttctggccct gaggccttct 300
gatgagggca cctatgagtg cgtggtgctg aagtacgaga aggacgcctt caagcgcgag 360
cacctggctg aagtgacact gtccgtgaag gccgactttc ccacaccttc catctccgac 420
ttcgagatcc ctacctccaa catccggcgg atcatctgtt ctacctctgg cggctttcct 480
gagcctcacc tgtcttggct ggaaaacggc gaggaactga acgccatcaa caccaccgtg 540
tctcaggacc ccgaaaccga gctgtacgct gtgtcctcca agctggactt caacatgacc 600
accaaccaca gcttcatgtg cctgattaag tacggccacc tgagagtgaa ccagaccttc 660
aactggaaca ccaccaagca agagcacttc cctgacaatg gatctggcgg cggaggttct 720
ggcggaggtg gaagcggagg cggaggatct gctgagtcta agtatggccc tccttgtcct 780
ccatgtcctg ctccagaagc tgctggcgga ccctctgtgt tcctgtttcc tccaaagcct 840
aaggaccagc tcatgatctc tcggacaccc gaagtgacct gcgtggtggt ggatgtgtct 900
caagaggacc ctgaggtgca gttcaattgg tacgtggacg gcgtggaagt gcacaacgcc 960
aagaccaagc ctagagagga acagttcaac tccacctaca gagtggtgtc cgtgctgacc 1020
gtgctgcacc aggattggct gaacggcaaa gagtacaagt gcaaggtgtc caacaagggc 1080
ctgccttcca gcatcgaaaa gaccatctcc aaggctaagg gccagcctag ggaaccccag 1140
gtttacaccc tgcctccaag ccaagaggaa atgaccaaga accaggtgtc cctgacctgc 1200
ctggtcaagg gcttctaccc ttccgacatt gccgtggaat gggagtccaa tggccagcct 1260
gagaacaact acaagaccac acctcctgtg ctggactccg acggctcctt ctttctgtac 1320
tctcgcctga ccgtggacaa gtctagatgg caagagggca acgtgttctc ctgctctgtg 1380
ctgcacgagg ccctgcacaa tcactacacc cagaagtccc tgtctctgtc tcttggaggt 1440
ggtggcggtt ctgcccctac cagctcctct accaagaaaa cccagctcca gttggagcat 1500
ctgctgctgg acctccagat gattctgaac gggatcaaca actataagaa ccccaagctg 1560
accgccatgc tgaccgctaa gttctacatg cccaagaagg ccaccgagct gaagcacctc 1620
cagtgcctgg aagaagaact gaagcccctg gaagaggtgc tgaatggggc ccagtccaag 1680
aacttccacc tgaggccacg ggacctgatc agcaacatca acgtgatcgt gctggaactg 1740
aagggctccg agacaacctt tatgtgcgag tacgccgacg agacagccac catcgtggaa 1800
tttctgaacc ggtggatcac cttctgccag agcatcatct ccacactgac ctgatga 1857
<210> 30
<211> 592
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 融合蛋白 (GI102-M72)
<400> 30
Val Ile His Val Thr Lys Glu Val Lys Glu Val Ala Thr Leu Ser Cys
1 5 1015
Gly His Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg Ile Tyr Trp
202530
Gln Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn
354045
Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn
505560
Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr
65707580
Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His
859095
Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro Ser
100 105 110
Ile Ser Asp Phe Glu Ile Pro Thr Ser Asn Ile Arg Arg Ile Ile Cys
115 120 125
Ser Thr Ser Gly Gly Phe Pro Glu Pro His Leu Ser Trp Leu Glu Asn
130 135 140
Gly Glu Glu Leu Asn Ala Ile Asn Thr Thr Val Ser Gln Asp Pro Glu
145 150 155 160
Thr Glu Leu Tyr Ala Val Ser Ser Lys Leu Asp Phe Asn Met Thr Thr
165 170 175
Asn His Ser Phe Met Cys Leu Ile Lys Tyr Gly His Leu Arg Val Asn
180 185 190
Gln Thr Phe Asn Trp Asn Thr Thr Lys Gln Glu His Phe Pro Asp Asn
195 200 205
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
210 215 220
Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
225 230 235 240
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
245 250 255
Asp Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
260 265 270
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
275 280 285
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
290 295 300
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
305 310 315 320
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
325 330 335
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
340 345 350
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
355 360 365
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
370 375 380
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
385 390 395 400
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
405 410 415
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
420 425 430
Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
435 440 445
Leu Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser
450 455 460
Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu
465 470 475 480
Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr
485 490 495
Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu
500 505 510
Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val
515 520 525
Leu Asn Gly Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu
530 535 540
Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr
545 550 555 560
Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe
565 570 575
Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
580 585 590
<210> 31
<211> 1851
<212> DNA
<213> 人工序列（Artificial Sequence）
<220>
<223> 编码融合蛋白(GI101w)的核苷酸
<400> 31
atggatgcta tgctgagagg cctgtgttgc gtgctgctgc tgtgtggcgc tgtgttcgtg 60
tctccttctc acgctgtgat ccacgtgacc aaagaagtga aagaggtcgc cacactgtcc 120
tgcggccaca acgtttcagt ggaagaactg gcccagacca ggatctactg gcagaaagaa 180
aagaaaatgg tgctgaccat gatgtccggc gacatgaaca tctggcctga gtacaagaac 240
cggaccatct tcgacatcac caacaacctg tccatcgtga ttctggccct gaggccttct 300
gatgagggca cctatgagtg cgtggtgctg aagtacgaga aggacgcctt caagcgcgag 360
cacctggctg aagtgacact gtccgtgaag gccgactttc ccacaccttc catctccgac 420
ttcgagatcc ctacctccaa catccggcgg atcatctgtt ctacctctgg cggctttcct 480
gagcctcacc tgtcttggct ggaaaacggc gaggaactga acgccatcaa caccaccgtg 540
tctcaggacc ccgaaaccga gctgtacgct gtgtcctcca agctggactt caacatgacc 600
accaaccaca gcttcatgtg cctgattaag tacggccacc tgagagtgaa ccagaccttc 660
aactggaaca ccaccaagca agagcacttc cctgacaatg gatctggcgg cggaggttct 720
ggcggaggtg gaagcggagg cggaggatct gctgagtcta agtatggccc tccttgtcct 780
ccatgtcctg ctccagaagc tgctggcgga ccctctgtgt tcctgtttcc tccaaagcct 840
aaggaccagc tcatgatctc tcggacaccc gaagtgacct gcgtggtggt ggatgtgtct 900
caagaggacc ctgaggtgca gttcaattgg tacgtggacg gcgtggaagt gcacaacgcc 960
aagaccaagc ctagagagga acagttcaac tccacctaca gagtggtgtc cgtgctgacc 1020
gtgctgcacc aggattggct gaacggcaaa gagtacaagt gcaaggtgtc caacaagggc 1080
ctgccttcca gcatcgaaaa gaccatctcc aaggctaagg gccagcctag ggaaccccag 1140
gtttacaccc tgcctccaag ccaagaggaa atgaccaaga accaggtgtc cctgacctgc 1200
ctggtcaagg gcttctaccc ttccgacatt gccgtggaat gggagtccaa tggccagcct 1260
gagaacaact acaagaccac acctcctgtg ctggactccg acggctcctt ctttctgtac 1320
tctcgcctga ccgtggacaa gtctagatgg caagagggca acgtgttctc ctgctctgtg 1380
ctgcacgagg ccctgcacaa tcactacacc cagaagtccc tgtctctgtc tcttggaggt 1440
ggtggcggtt ctgcccctac cagctcctct accaagaaaa cccagctcca gttggagcat 1500
ctgctgctgg acctccagat gattctgaac gggatcaaca actataagaa ccccaagctg 1560
acccgcatgc tgacctttaa gttctacatg cccaagaagg ccaccgagct gaagcacctc 1620
cagtgcctgg aagaagaact gaagcccctg gaagaggtgc tgaatctggc ccagtccaag 1680
aacttccacc tgaggccacg ggacctgatc agcaacatca acgtgatcgt gctggaactg 1740
aagggctccg agacaacctt tatgtgcgag tacgccgacg agacagccac catcgtggaa 1800
tttctgaacc ggtggatcac cttctgccag agcatcatct ccacactgac c 1851
<210> 32
<211> 592
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 融合蛋白 (GI101w)
<400> 32
Val Ile His Val Thr Lys Glu Val Lys Glu Val Ala Thr Leu Ser Cys
1 5 1015
Gly His Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg Ile Tyr Trp
202530
Gln Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn
354045
Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn
505560
Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr
65707580
Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His
859095
Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro Ser
100 105 110
Ile Ser Asp Phe Glu Ile Pro Thr Ser Asn Ile Arg Arg Ile Ile Cys
115 120 125
Ser Thr Ser Gly Gly Phe Pro Glu Pro His Leu Ser Trp Leu Glu Asn
130 135 140
Gly Glu Glu Leu Asn Ala Ile Asn Thr Thr Val Ser Gln Asp Pro Glu
145 150 155 160
Thr Glu Leu Tyr Ala Val Ser Ser Lys Leu Asp Phe Asn Met Thr Thr
165 170 175
Asn His Ser Phe Met Cys Leu Ile Lys Tyr Gly His Leu Arg Val Asn
180 185 190
Gln Thr Phe Asn Trp Asn Thr Thr Lys Gln Glu His Phe Pro Asp Asn
195 200 205
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
210 215 220
Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
225 230 235 240
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
245 250 255
Asp Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
260 265 270
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
275 280 285
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
290 295 300
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
305 310 315 320
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
325 330 335
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
340 345 350
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
355 360 365
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
370 375 380
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
385 390 395 400
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
405 410 415
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
420 425 430
Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
435 440 445
Leu Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser
450 455 460
Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu
465 470 475 480
Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr
485 490 495
Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu
500 505 510
Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val
515 520 525
Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu
530 535 540
Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr
545 550 555 560
Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe
565 570 575
Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
580 585 590
<210> 33
<211> 1848
<212> DNA
<213> 人工序列（Artificial Sequence）
<220>
<223> 编码融合蛋白(mGI102-M61)的核苷酸
<400> 33
atggatgcta tgctgagagg cctgtgttgc gtgctgctgc tgtgtggcgc tgtgttcgtg 60
tctccttctc acgctgtgga cgagcagctc tccaagtccg tgaaggataa ggtcctgctg 120
ccttgccggt acaactctcc tcacgaggac gagtctgagg accggatcta ctggcagaaa 180
cacgacaagg tggtgctgtc cgtgatcgcc ggaaagctga aagtgtggcc tgagtacaag 240
aacaggaccc tgtacgacaa caccacctac agcctgatca tcctgggcct cgtgctgagc 300
gatagaggca cctattcttg cgtggtgcag aagaaagagc ggggcaccta cgaagtgaag 360
cacctggctc tggtcaagct gtccatcaag gccgacttca gcacccctaa catcaccgag 420
tctggcaacc cttccgccga caccaagaga atcacctgtt tcgcctctgg cggcttccct 480
aagcctcggt tctcttggct ggaaaacggc agagagctgc ccggcatcaa taccaccatt 540
tctcaggacc cagagtccga gctgtacacc atctccagcc agctcgactt taacaccacc 600
agaaaccaca ccatcaagtg cctgattaag tacggcgacg cccacgtgtc cgaggacttt 660
acttgggaga aacctcctga ggaccctcct gactctggat ctggcggcgg aggttctggc 720
ggaggtggaa gcggaggcgg aggatctgct gagtctaagt atggccctcc ttgtcctcca 780
tgtcctgctc cagaagctgc tggcggaccc tctgtgttcc tgtttcctcc aaagcctaag 840
gaccagctca tgatctctcg gacccctgaa gtgacctgcg tggtggtgga tgtgtctcaa 900
gaggaccctg aggtgcagtt caattggtac gtggacggcg tggaagtgca caacgccaag 960
accaagccta gagaggaaca gttcaactcc acctatagag tggtgtccgt gctgaccgtg 1020
ctgcaccagg attggctgaa cggcaaagag tacaagtgca aggtgtccaa caagggcctg 1080
ccttccagca tcgaaaagac catcagcaag gctaagggcc agcctaggga accccaggtt 1140
tacaccctgc ctccaagcca agaggaaatg accaagaacc aggtgtccct gacctgcctg 1200
gtcaagggct tctacccttc cgacattgcc gtggaatggg agtccaatgg ccagcctgag 1260
aacaactaca agaccacacc tcctgtgctg gactccgacg gctccttctt tctgtactct 1320
cgcctgaccg tggacaagtc taggtggcaa gagggcaacg tgttctcctg ctctgtgctg 1380
cacgaggctc tgcacaacca ctacacccag aagtccctgt ctctgtctct tggaggtggt 1440
ggcggttctg cccctacctc cagctctacc aagaaaaccc agctccagtt ggagcatctg 1500
ctgctggacc tccagatgat cctgaatggc atcaacaatt acaagaaccc caagctgacc 1560
gccatgctga ccgctaagtt ctacatgccc aagaaggcca ccgagctgaa gcacttgcag 1620
tgcctggaaa gggaactgaa gcccctggaa gaagtgctga atctggccca gtccaagaac 1680
ttccacctga ggcctaggga cctgatctcc aacatcaacg tgatcgtgct ggaactgaaa 1740
ggctccgaga caaccttcat gtgcgagtac gccgacgaga cagccaccat cgtggaattt 1800
ctgaaccggt ggatcacctt ctgccagagc atcatctcca cactgacc 1848
<210> 34
<211> 616
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 融合蛋白 (mGI102-M61)
<400> 34
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Asp Glu Gln Leu Ser Lys
202530
Ser Val Lys Asp Lys Val Leu Leu Pro Cys Arg Tyr Asn Ser Pro His
354045
Glu Asp Glu Ser Glu Asp Arg Ile Tyr Trp Gln Lys His Asp Lys Val
505560
Val Leu Ser Val Ile Ala Gly Lys Leu Lys Val Trp Pro Glu Tyr Lys
65707580
Asn Arg Thr Leu Tyr Asp Asn Thr Thr Tyr Ser Leu Ile Ile Leu Gly
859095
Leu Val Leu Ser Asp Arg Gly Thr Tyr Ser Cys Val Val Gln Lys Lys
100 105 110
Glu Arg Gly Thr Tyr Glu Val Lys His Leu Ala Leu Val Lys Leu Ser
115 120 125
Ile Lys Ala Asp Phe Ser Thr Pro Asn Ile Thr Glu Ser Gly Asn Pro
130 135 140
Ser Ala Asp Thr Lys Arg Ile Thr Cys Phe Ala Ser Gly Gly Phe Pro
145 150 155 160
Lys Pro Arg Phe Ser Trp Leu Glu Asn Gly Arg Glu Leu Pro Gly Ile
165 170 175
Asn Thr Thr Ile Ser Gln Asp Pro Glu Ser Glu Leu Tyr Thr Ile Ser
180 185 190
Ser Gln Leu Asp Phe Asn Thr Thr Arg Asn His Thr Ile Lys Cys Leu
195 200 205
Ile Lys Tyr Gly Asp Ala His Val Ser Glu Asp Phe Thr Trp Glu Lys
210 215 220
Pro Pro Glu Asp Pro Pro Asp Ser Gly Ser Gly Gly Gly Gly Ser Gly
225 230 235 240
Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro
245 250 255
Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val
260 265 270
Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg Thr
275 280 285
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
290 295 300
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
305 310 315 320
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
325 330 335
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
340 345 350
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
355 360 365
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
370 375 380
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
385 390 395 400
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
405 410 415
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
420 425 430
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
435 440 445
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala Leu
450 455 460
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly
465 470 475 480
Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln
485 490 495
Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn
500 505 510
Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr
515 520 525
Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Arg
530 535 540
Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn
545 550 555 560
Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val
565 570 575
Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp
580 585 590
Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys
595 600 605
Gln Ser Ile Ile Ser Thr Leu Thr
610 615
<210> 35
<211> 153
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 野生型hIL-2
<400> 35
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 1015
Val Thr Asn Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu
202530
Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile
354045
Asn Asn Tyr Lys Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe
505560
Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu
65707580
Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys
859095
Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile
100 105 110
Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala
115 120 125
Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe
130 135 140
Cys Gln Ser Ile Ile Ser Thr Leu Thr
145 150
<210> 36
<211> 158
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 具有信号序列的IL-2
<400> 36
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Ala Pro Thr Ser Ser Ser Thr
202530
Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met
354045
Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Arg Met
505560
Leu Thr Phe Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His
65707580
Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn
859095
Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser
100 105 110
Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe
115 120 125
Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn
130 135 140
Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
145 150 155
<210> 37
<211> 474
<212> DNA
<213> 人工序列（Artificial Sequence）
<220>
<223> 编码具有信号序列的IL-2的核酸序列
<400> 37
atggatgcta tgctgagagg cctgtgttgc gtgctgctgc tgtgtggcgc tgtgttcgtg 60
tctccttctc acgctgcccc taccagctcc tctaccaaga aaacccagct ccagttggag 120
catctgctgc tggacctcca gatgattctg aacgggatca acaactataa gaaccccaag 180
ctgacccgca tgctgacctt taagttctac atgcccaaga aggccaccga gctgaagcac 240
ctccagtgcc tggaagaaga actgaagccc ctggaagagg tgctgaatct ggcccagtcc 300
aagaacttcc acctgaggcc acgggacctg atcagcaaca tcaacgtgat cgtgctggaa 360
ctgaagggct ccgagacaac ctttatgtgc gagtacgccg acgagacagc caccatcgtg 420
gaatttctga accggtggat caccttctgc cagagcatca tctccacact gacc 474
<210> 38
<211> 222
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体1
<400> 38
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp
210 215 220
<210> 39
<211> 606
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P1
<400> 39
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Gly Ser
210 215 220
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala
225 230 235 240
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala
245 250 255
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln
260 265 270
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
275 280 285
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val
290 295 300
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser
305 310 315 320
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
325 330 335
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser
340 345 350
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
355 360 365
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln
370 375 380
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
385 390 395 400
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
405 410 415
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu
420 425 430
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser
435 440 445
Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
450 455 460
Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr
465 470 475 480
Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met
485 490 495
Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met
500 505 510
Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His
515 520 525
Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn
530 535 540
Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser
545 550 555 560
Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe
565 570 575
Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn
580 585 590
Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
595 600 605
<210> 40
<211> 215
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体2
<400> 40
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg
210 215
<210> 41
<211> 606
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P2
<400> 41
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Gly Ser
210 215 220
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala
225 230 235 240
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala
245 250 255
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln
260 265 270
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
275 280 285
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val
290 295 300
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser
305 310 315 320
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
325 330 335
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser
340 345 350
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
355 360 365
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln
370 375 380
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
385 390 395 400
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
405 410 415
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu
420 425 430
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser
435 440 445
Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
450 455 460
Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr
465 470 475 480
Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met
485 490 495
Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met
500 505 510
Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His
515 520 525
Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn
530 535 540
Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser
545 550 555 560
Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe
565 570 575
Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn
580 585 590
Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
595 600 605
<210> 42
<211> 210
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体3
<400> 42
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys
210
<210> 43
<211> 594
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P3
<400> 43
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
210 215 220
Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro
225 230 235 240
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
245 250 255
Pro Lys Asp Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
260 265 270
Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr
275 280 285
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
290 295 300
Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
305 310 315 320
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
325 330 335
Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
340 345 350
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met
355 360 365
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
370 375 380
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
385 390 395 400
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
405 410 415
Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val
420 425 430
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln
435 440 445
Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr
450 455 460
Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu
465 470 475 480
Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys
485 490 495
Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr
500 505 510
Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu
515 520 525
Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg
530 535 540
Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser
545 550 555 560
Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val
565 570 575
Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr
580 585 590
Leu Thr
<210> 44
<211> 202
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体4
<400> 44
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn
195 200
<210> 45
<211> 586
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P4
<400> 45
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn Gly Ser Gly Gly Gly Gly
195 200 205
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr
210 215 220
Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp
260 265 270
Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln
450 455 460
Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly
465 470 475 480
Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys
485 490 495
Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu
500 505 510
Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser
515 520 525
Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val
530 535 540
Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr
545 550 555 560
Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr
565 570 575
Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
580 585
<210> 46
<211> 199
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体5
<400> 46
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met
195
<210> 47
<211> 583
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P5
<400> 47
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Gly Ser Gly Gly Gly Gly Ser Gly Gly
195 200 205
Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro Pro
210 215 220
Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe
225 230 235 240
Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg Thr Pro
245 250 255
Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val
260 265 270
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
275 280 285
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val
290 295 300
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
305 310 315 320
Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser
325 330 335
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
340 345 350
Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
355 360 365
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
370 375 380
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp
385 390 395 400
Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp
405 410 415
Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala Leu His
420 425 430
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly Gly
435 440 445
Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu
450 455 460
Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn
465 470 475 480
Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met
485 490 495
Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu
500 505 510
Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe
515 520 525
His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu
530 535 540
Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu
545 550 555 560
Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln
565 570 575
Ser Ile Ile Ser Thr Leu Thr
580
<210> 48
<211> 187
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体6
<400> 48
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu
180 185
<210> 49
<211> 571
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P6
<400> 49
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Gly Ser Gly Gly Gly
180 185 190
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys
195 200 205
Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly
210 215 220
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile
225 230 235 240
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu
245 250 255
Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
260 265 270
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg
275 280 285
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
290 295 300
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu
305 310 315 320
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
325 330 335
Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu
340 345 350
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
355 360 365
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
370 375 380
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp
385 390 395 400
Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His
405 410 415
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu
420 425 430
Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr
435 440 445
Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn
450 455 460
Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala
465 470 475 480
Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys
485 490 495
Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln
500 505 510
Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn
515 520 525
Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu
530 535 540
Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile
545 550 555 560
Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
565 570
<210> 50
<211> 183
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体7
<400> 50
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp
180
<210> 51
<211> 567
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P7
<400> 51
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Gly Ser Gly Gly Gly Gly Ser Gly Gly
180 185 190
Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro Pro
195 200 205
Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe
210 215 220
Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg Thr Pro
225 230 235 240
Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val
245 250 255
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
260 265 270
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val
275 280 285
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
290 295 300
Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser
305 310 315 320
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
325 330 335
Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
340 345 350
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
355 360 365
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp
370 375 380
Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp
385 390 395 400
Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala Leu His
405 410 415
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly Gly
420 425 430
Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu
435 440 445
Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn
450 455 460
Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met
465 470 475 480
Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu
485 490 495
Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe
500 505 510
His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu
515 520 525
Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu
530 535 540
Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln
545 550 555 560
Ser Ile Ile Ser Thr Leu Thr
565
<210> 52
<211> 175
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体8
<400> 52
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala
165 170 175
<210> 53
<211> 559
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P8
<400> 53
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Gly
165 170 175
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
180 185 190
Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu
195 200 205
Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
210 215 220
Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
225 230 235 240
Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly
245 250 255
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn
260 265 270
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
275 280 285
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro
290 295 300
Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
305 310 315 320
Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn
325 330 335
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
340 345 350
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
355 360 365
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg
370 375 380
Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys
385 390 395 400
Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
405 410 415
Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser
420 425 430
Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln
435 440 445
Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala
450 455 460
Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys
465 470 475 480
His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu
485 490 495
Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile
500 505 510
Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr
515 520 525
Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu
530 535 540
Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
545 550 555
<210> 54
<211> 136
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体9
<400> 54
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro
130 135
<210> 55
<211> 520
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P9
<400> 55
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Gly Ser Gly Gly Gly Gly Ser Gly
130 135 140
Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro
145 150 155 160
Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val
165 170 175
Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg Thr
180 185 190
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
195 200 205
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
210 215 220
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
225 230 235 240
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
245 250 255
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
260 265 270
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
275 280 285
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
290 295 300
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
305 310 315 320
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
325 330 335
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
340 345 350
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala Leu
355 360 365
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly
370 375 380
Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln
385 390 395 400
Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn
405 410 415
Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr
420 425 430
Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu
435 440 445
Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn
450 455 460
Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val
465 470 475 480
Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp
485 490 495
Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys
500 505 510
Gln Ser Ile Ile Ser Thr Leu Thr
515 520
<210> 56
<211> 130
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体10
<400> 56
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Glu Val Lys Glu Val Ala Thr
202530
Leu Ser Cys Gly His Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg
354045
Ile Tyr Trp Gln Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly
505560
Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile
65707580
Thr Asn Asn Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu
859095
Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys
100 105 110
Arg Glu His Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro
115 120 125
Thr Pro
130
<210> 57
<211> 514
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P10
<400> 57
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Glu Val Lys Glu Val Ala Thr
202530
Leu Ser Cys Gly His Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg
354045
Ile Tyr Trp Gln Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly
505560
Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile
65707580
Thr Asn Asn Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu
859095
Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys
100 105 110
Arg Glu His Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro
115 120 125
Thr Pro Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
130 135 140
Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro
145 150 155 160
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
165 170 175
Pro Lys Asp Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
180 185 190
Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr
195 200 205
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
210 215 220
Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
225 230 235 240
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
245 250 255
Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
260 265 270
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met
275 280 285
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
290 295 300
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
305 310 315 320
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
325 330 335
Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val
340 345 350
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln
355 360 365
Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr
370 375 380
Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu
385 390 395 400
Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys
405 410 415
Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr
420 425 430
Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu
435 440 445
Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg
450 455 460
Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser
465 470 475 480
Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val
485 490 495
Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr
500 505 510
Leu Thr
<210> 58
<211> 125
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体11
<400> 58
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Ala Thr Leu Ser Cys Gly His
202530
Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys
354045
Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp
505560
Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser
65707580
Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys
859095
Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala
100 105 110
Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro
115 120 125
<210> 59
<211> 509
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P11
<400> 59
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Ala Thr Leu Ser Cys Gly His
202530
Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys
354045
Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp
505560
Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser
65707580
Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys
859095
Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala
100 105 110
Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro Gly Ser Gly
115 120 125
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu
130 135 140
Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala
145 150 155 160
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu
165 170 175
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
180 185 190
Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
195 200 205
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr
210 215 220
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
225 230 235 240
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser
245 250 255
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
260 265 270
Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val
275 280 285
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
290 295 300
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
305 310 315 320
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr
325 330 335
Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val
340 345 350
Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
355 360 365
Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys
370 375 380
Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile
385 390 395 400
Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu
405 410 415
Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu
420 425 430
Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu
435 440 445
Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn
450 455 460
Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met
465 470 475 480
Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg
485 490 495
Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
500 505
<210> 60
<211> 116
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体12
<400> 60
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Ser Val Glu Glu Leu Ala Gln
202530
Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val Leu Thr Met Met
354045
Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe
505560
Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser
65707580
Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala
859095
Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp
100 105 110
Phe Pro Thr Pro
115
<210> 61
<211> 500
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P12
<400> 61
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Ser Val Glu Glu Leu Ala Gln
202530
Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val Leu Thr Met Met
354045
Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe
505560
Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser
65707580
Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala
859095
Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp
100 105 110
Phe Pro Thr Pro Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
115 120 125
Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro
130 135 140
Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro
145 150 155 160
Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr
165 170 175
Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn
180 185 190
Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg
195 200 205
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val
210 215 220
Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser
225 230 235 240
Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys
245 250 255
Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu
260 265 270
Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
275 280 285
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
290 295 300
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
305 310 315 320
Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly
325 330 335
Asn Val Phe Ser Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr
340 345 350
Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala
355 360 365
Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu
370 375 380
Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn
385 390 395 400
Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys
405 410 415
Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro
420 425 430
Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg
435 440 445
Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys
450 455 460
Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr
465 470 475 480
Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile
485 490 495
Ser Thr Leu Thr
500
<210> 62
<211> 110
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体13
<400> 62
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Gln Thr Arg Ile Tyr Trp Gln
202530
Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn Ile
354045
Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu
505560
Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu
65707580
Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His Leu
859095
Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro
100 105 110
<210> 63
<211> 494
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P13
<400> 63
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Gln Thr Arg Ile Tyr Trp Gln
202530
Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn Ile
354045
Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu
505560
Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu
65707580
Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His Leu
859095
Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro Gly Ser
100 105 110
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala
115 120 125
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala
130 135 140
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln
145 150 155 160
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
165 170 175
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val
180 185 190
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser
195 200 205
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
210 215 220
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser
225 230 235 240
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
245 250 255
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln
260 265 270
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
275 280 285
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
290 295 300
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu
305 310 315 320
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser
325 330 335
Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
340 345 350
Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr
355 360 365
Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met
370 375 380
Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met
385 390 395 400
Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His
405 410 415
Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn
420 425 430
Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser
435 440 445
Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe
450 455 460
Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn
465 470 475 480
Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
485 490
<210> 64
<211> 103
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体14
<400> 64
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Gln Thr Arg Ile Tyr Trp Gln
202530
Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn Ile
354045
Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu
505560
Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu
65707580
Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His Leu
859095
Ala Glu Val Thr Leu Ser Val
100
<210> 65
<211> 487
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P14
<400> 65
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Gln Thr Arg Ile Tyr Trp Gln
202530
Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn Ile
354045
Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu
505560
Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu
65707580
Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His Leu
859095
Ala Glu Val Thr Leu Ser Val Gly Ser Gly Gly Gly Gly Ser Gly Gly
100 105 110
Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro Pro
115 120 125
Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe
130 135 140
Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg Thr Pro
145 150 155 160
Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val
165 170 175
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
180 185 190
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val
195 200 205
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
210 215 220
Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser
225 230 235 240
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
245 250 255
Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
260 265 270
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
275 280 285
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp
290 295 300
Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp
305 310 315 320
Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala Leu His
325 330 335
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly Gly
340 345 350
Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu
355 360 365
Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn
370 375 380
Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met
385 390 395 400
Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu
405 410 415
Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe
420 425 430
His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu
435 440 445
Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu
450 455 460
Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln
465 470 475 480
Ser Ile Ile Ser Thr Leu Thr
485
<210> 66
<211> 93
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体15
<400> 66
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Ser Gly Asp Met Asn Ile Trp
202530
Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser
354045
Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys
505560
Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala
65707580
Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro
8590
<210> 67
<211> 477
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P15
<400> 67
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Ser Gly Asp Met Asn Ile Trp
202530
Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser
354045
Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys
505560
Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala
65707580
Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro Gly Ser Gly
859095
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu
100 105 110
Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala
115 120 125
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu
130 135 140
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
145 150 155 160
Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
165 170 175
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr
180 185 190
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
195 200 205
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser
210 215 220
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
225 230 235 240
Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val
245 250 255
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
260 265 270
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
275 280 285
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr
290 295 300
Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val
305 310 315 320
Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
325 330 335
Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys
340 345 350
Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile
355 360 365
Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu
370 375 380
Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu
385 390 395 400
Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu
405 410 415
Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn
420 425 430
Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met
435 440 445
Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg
450 455 460
Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
465 470 475
<210> 68
<211> 49
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体16
<400> 68
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Gln Thr Arg Ile Tyr Trp Gln
202530
Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn Ile
354045
Trp
<210> 69
<211> 433
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P16
<400> 69
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Gln Thr Arg Ile Tyr Trp Gln
202530
Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn Ile
354045
Trp Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
505560
Gly Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala
65707580
Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
859095
Lys Asp Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
100 105 110
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val
115 120 125
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
130 135 140
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
145 150 155 160
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly
165 170 175
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
180 185 190
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr
195 200 205
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
210 215 220
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
225 230 235 240
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
245 250 255
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe
260 265 270
Ser Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys
275 280 285
Ser Leu Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser
290 295 300
Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp
305 310 315 320
Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu
325 330 335
Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu
340 345 350
Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu
355 360 365
Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp
370 375 380
Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu
385 390 395 400
Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu
405 410 415
Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu
420 425 430
Thr
<210> 70
<211> 42
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体17
<400> 70
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Gln Thr Arg Ile Tyr Trp Gln
202530
Lys Glu Lys Lys Met Val Leu Thr Met Met
3540
<210> 71
<211> 426
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P17
<400> 71
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Gln Thr Arg Ile Tyr Trp Gln
202530
Lys Glu Lys Lys Met Val Leu Thr Met Met Gly Ser Gly Gly Gly Gly
354045
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr
505560
Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro
65707580
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser
859095
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp
100 105 110
Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
115 120 125
Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val
130 135 140
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
145 150 155 160
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys
165 170 175
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
180 185 190
Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
195 200 205
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
210 215 220
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
225 230 235 240
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys
245 250 255
Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu
260 265 270
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
275 280 285
Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln
290 295 300
Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly
305 310 315 320
Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys
325 330 335
Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu
340 345 350
Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser
355 360 365
Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val
370 375 380
Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr
385 390 395 400
Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr
405 410 415
Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
420 425
<210> 72
<211> 52
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体18
<400> 72
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Gly Thr Tyr Glu Cys Val Val
202530
Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val
354045
Thr Leu Ser Val
50
<210> 73
<211> 436
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P18
<400> 73
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Gly Thr Tyr Glu Cys Val Val
202530
Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val
354045
Thr Leu Ser Val Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
505560
Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro
65707580
Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro
859095
Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr
100 105 110
Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn
115 120 125
Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg
130 135 140
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val
145 150 155 160
Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser
165 170 175
Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys
180 185 190
Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu
195 200 205
Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
210 215 220
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
225 230 235 240
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
245 250 255
Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly
260 265 270
Asn Val Phe Ser Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr
275 280 285
Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala
290 295 300
Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu
305 310 315 320
Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn
325 330 335
Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys
340 345 350
Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro
355 360 365
Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg
370 375 380
Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys
385 390 395 400
Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr
405 410 415
Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile
420 425 430
Ser Thr Leu Thr
435
<210> 74
<211> 233
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-CD80
<400> 74
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn
225 230
<210> 75
<211> 612
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P19
<400> 75
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Gly Ser Gly Gly Gly Gly Ser
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly
245 250 255
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
260 265 270
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg
275 280 285
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
290 295 300
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
305 310 315 320
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
325 330 335
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
340 345 350
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
355 360 365
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
370 375 380
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
385 390 395 400
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
405 410 415
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
420 425 430
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
435 440 445
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala
450 455 460
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Ala
465 470 475 480
Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu
485 490 495
Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn
500 505 510
Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys
515 520 525
Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro
530 535 540
Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg
545 550 555 560
Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys
565 570 575
Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr
580 585 590
Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile
595 600 605
Ser Thr Leu Thr
610
<210> 76
<211> 5
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头2变体20
<400> 76
Glu Ala Ala Ala Lys
1 5
<210> 77
<211> 617
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P20
<400> 77
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Gly Ser Gly Gly Gly Gly Ser
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly
245 250 255
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
260 265 270
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg
275 280 285
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
290 295 300
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
305 310 315 320
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
325 330 335
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
340 345 350
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
355 360 365
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
370 375 380
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
385 390 395 400
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
405 410 415
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
420 425 430
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
435 440 445
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala
450 455 460
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Glu
465 470 475 480
Ala Ala Ala Lys Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu
485 490 495
Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile
500 505 510
Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe
515 520 525
Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu
530 535 540
Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys
545 550 555 560
Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile
565 570 575
Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala
580 585 590
Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe
595 600 605
Cys Gln Ser Ile Ile Ser Thr Leu Thr
610 615
<210> 78
<211> 10
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头2变体21
<400> 78
Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys
1 5 10
<210> 79
<211> 622
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P21
<400> 79
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Gly Ser Gly Gly Gly Gly Ser
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly
245 250 255
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
260 265 270
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg
275 280 285
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
290 295 300
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
305 310 315 320
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
325 330 335
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
340 345 350
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
355 360 365
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
370 375 380
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
385 390 395 400
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
405 410 415
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
420 425 430
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
435 440 445
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala
450 455 460
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Glu
465 470 475 480
Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Pro Thr Ser Ser Ser Thr
485 490 495
Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met
500 505 510
Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met
515 520 525
Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His
530 535 540
Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn
545 550 555 560
Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser
565 570 575
Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe
580 585 590
Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn
595 600 605
Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
610 615 620
<210> 80
<211> 20
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头2变体22
<400> 80
Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Glu
1 5 1015
Ala Ala Ala Lys
20
<210> 81
<211> 632
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P22
<400> 81
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Gly Ser Gly Gly Gly Gly Ser
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly
245 250 255
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
260 265 270
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg
275 280 285
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
290 295 300
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
305 310 315 320
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
325 330 335
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
340 345 350
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
355 360 365
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
370 375 380
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
385 390 395 400
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
405 410 415
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
420 425 430
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
435 440 445
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala
450 455 460
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Glu
465 470 475 480
Ala Ala Ala Lys Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Glu Ala
485 490 495
Ala Ala Lys Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln
500 505 510
Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn
515 520 525
Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr
530 535 540
Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu
545 550 555 560
Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn
565 570 575
Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val
580 585 590
Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp
595 600 605
Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys
610 615 620
Gln Ser Ile Ile Ser Thr Leu Thr
625 630
<210> 82
<211> 10
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头2变体23
<400> 82
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10
<210> 83
<211> 622
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P23
<400> 83
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Gly Ser Gly Gly Gly Gly Ser
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly
245 250 255
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
260 265 270
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg
275 280 285
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
290 295 300
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
305 310 315 320
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
325 330 335
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
340 345 350
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
355 360 365
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
370 375 380
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
385 390 395 400
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
405 410 415
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
420 425 430
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
435 440 445
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala
450 455 460
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly
465 470 475 480
Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr
485 490 495
Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met
500 505 510
Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met
515 520 525
Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His
530 535 540
Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn
545 550 555 560
Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser
565 570 575
Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe
580 585 590
Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn
595 600 605
Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
610 615 620
<210> 84
<211> 20
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头2变体24
<400> 84
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 1015
Gly Gly Gly Ser
20
<210> 85
<211> 632
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P24
<400> 85
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Gly Ser Gly Gly Gly Gly Ser
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly
245 250 255
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
260 265 270
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg
275 280 285
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
290 295 300
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
305 310 315 320
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
325 330 335
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
340 345 350
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
355 360 365
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
370 375 380
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
385 390 395 400
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
405 410 415
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
420 425 430
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
435 440 445
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala
450 455 460
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly
465 470 475 480
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln
500 505 510
Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn
515 520 525
Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr
530 535 540
Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu
545 550 555 560
Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn
565 570 575
Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val
580 585 590
Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp
595 600 605
Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys
610 615 620
Gln Ser Ile Ile Ser Thr Leu Thr
625 630
<210> 86
<211> 13
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头1变体25
<400> 86
Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro
1 5 10
<210> 87
<211> 600
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P25
<400> 87
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Ala Glu Ser Lys Tyr Gly Pro
225 230 235 240
Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val
245 250 255
Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg Thr
260 265 270
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
275 280 285
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
290 295 300
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
305 310 315 320
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
325 330 335
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
340 345 350
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
355 360 365
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
370 375 380
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
385 390 395 400
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
405 410 415
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
420 425 430
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala Leu
435 440 445
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly
450 455 460
Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln
465 470 475 480
Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn
485 490 495
Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr
500 505 510
Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu
515 520 525
Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn
530 535 540
Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val
545 550 555 560
Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp
565 570 575
Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys
580 585 590
Gln Ser Ile Ile Ser Thr Leu Thr
595 600
<210> 88
<211> 18
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头1变体26
<400> 88
Glu Ala Ala Ala Lys Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro
1 5 1015
Cys Pro
<210> 89
<211> 605
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P26
<400> 89
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Glu Ala Ala Ala Lys Ala Glu
225 230 235 240
Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala
245 250 255
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu
260 265 270
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
275 280 285
Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
290 295 300
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr
305 310 315 320
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
325 330 335
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser
340 345 350
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
355 360 365
Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val
370 375 380
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
385 390 395 400
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
405 410 415
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr
420 425 430
Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val
435 440 445
Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
450 455 460
Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys
465 470 475 480
Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile
485 490 495
Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu
500 505 510
Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu
515 520 525
Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu
530 535 540
Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn
545 550 555 560
Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met
565 570 575
Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg
580 585 590
Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
595 600 605
<210> 90
<211> 23
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头1变体27
<400> 90
Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Glu Ser Lys Tyr Gly
1 5 1015
Pro Pro Cys Pro Pro Cys Pro
20
<210> 91
<211> 610
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P27
<400> 91
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Glu Ala Ala Ala Lys Glu Ala
225 230 235 240
Ala Ala Lys Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro
245 250 255
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
260 265 270
Pro Lys Asp Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
275 280 285
Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr
290 295 300
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
305 310 315 320
Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
325 330 335
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
340 345 350
Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
355 360 365
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met
370 375 380
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
385 390 395 400
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
405 410 415
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
420 425 430
Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val
435 440 445
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln
450 455 460
Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr
465 470 475 480
Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu
485 490 495
Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys
500 505 510
Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr
515 520 525
Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu
530 535 540
Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg
545 550 555 560
Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser
565 570 575
Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val
580 585 590
Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr
595 600 605
Leu Thr
610
<210> 92
<211> 33
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头1变体28
<400> 92
Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Glu
1 5 1015
Ala Ala Ala Lys Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys
202530
Pro
<210> 93
<211> 620
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P28
<400> 93
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Glu Ala Ala Ala Lys Glu Ala
225 230 235 240
Ala Ala Lys Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Glu Ser
245 250 255
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
260 265 270
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met
275 280 285
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
290 295 300
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
305 310 315 320
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr
325 330 335
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
340 345 350
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
355 360 365
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
370 375 380
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser
385 390 395 400
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
405 410 415
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
420 425 430
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val
435 440 445
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu
450 455 460
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
465 470 475 480
Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys
485 490 495
Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu
500 505 510
Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr
515 520 525
Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln
530 535 540
Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala
545 550 555 560
Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile
565 570 575
Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys
580 585 590
Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp
595 600 605
Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
610 615 620
<210> 94
<211> 18
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头1变体29
<400> 94
Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro
1 5 1015
Cys Pro
<210> 95
<211> 605
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P29
<400> 95
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Gly Gly Gly Gly Ser Ala Glu
225 230 235 240
Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala
245 250 255
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu
260 265 270
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
275 280 285
Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
290 295 300
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr
305 310 315 320
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
325 330 335
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser
340 345 350
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
355 360 365
Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val
370 375 380
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
385 390 395 400
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
405 410 415
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr
420 425 430
Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val
435 440 445
Leu His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
450 455 460
Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys
465 470 475 480
Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile
485 490 495
Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu
500 505 510
Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu
515 520 525
Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu
530 535 540
Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn
545 550 555 560
Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met
565 570 575
Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg
580 585 590
Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
595 600 605
<210> 96
<211> 23
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头1变体30
<400> 96
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly
1 5 1015
Pro Pro Cys Pro Pro Cys Pro
20
<210> 97
<211> 610
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P30
<400> 97
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Gly Gly Gly Gly Ser Gly Gly
225 230 235 240
Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro
245 250 255
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
260 265 270
Pro Lys Asp Gln Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
275 280 285
Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr
290 295 300
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
305 310 315 320
Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
325 330 335
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
340 345 350
Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
355 360 365
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met
370 375 380
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
385 390 395 400
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
405 410 415
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
420 425 430
Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val
435 440 445
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln
450 455 460
Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr
465 470 475 480
Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu
485 490 495
Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys
500 505 510
Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr
515 520 525
Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu
530 535 540
Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg
545 550 555 560
Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser
565 570 575
Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val
580 585 590
Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr
595 600 605
Leu Thr
610
<210> 98
<211> 33
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头1变体31
<400> 98
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 1015
Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys
202530
Pro
<210> 99
<211> 620
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P31
<400> 99
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Gly Gly Gly Gly Ser Gly Gly
225 230 235 240
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser
245 250 255
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
260 265 270
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met
275 280 285
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
290 295 300
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val
305 310 315 320
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr
325 330 335
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
340 345 350
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
355 360 365
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
370 375 380
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser
385 390 395 400
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
405 410 415
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
420 425 430
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val
435 440 445
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Leu
450 455 460
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
465 470 475 480
Leu Gly Gly Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys
485 490 495
Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu
500 505 510
Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr
515 520 525
Ala Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln
530 535 540
Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala
545 550 555 560
Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile
565 570 575
Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys
580 585 590
Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp
595 600 605
Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
610 615 620
<210> 100
<211> 35
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头变体32
<400> 100
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
1 5 1015
Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Gly Gly
202530
Gly Gly Ser
35
<210> 101
<211> 404
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P32
<400> 101
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Gly Gly Gly Gly Ser Gly Gly
225 230 235 240
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser
245 250 255
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Gly Gly Gly Gly Ser Ala
260 265 270
Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu
275 280 285
Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn
290 295 300
Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys
305 310 315 320
Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro
325 330 335
Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg
340 345 350
Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys
355 360 365
Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr
370 375 380
Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile
385 390 395 400
Ser Thr Leu Thr
<210> 102
<211> 70
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头变体33
<400> 102
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
1 5 1015
Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Gly Gly
202530
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
354045
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
505560
Ser Gly Gly Gly Gly Ser
6570
<210> 103
<211> 439
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P33
<400> 103
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Gly Gly Gly Gly Ser Gly Gly
225 230 235 240
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser
245 250 255
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Gly Gly Gly Gly Ser Gly
260 265 270
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
275 280 285
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
290 295 300
Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu
305 310 315 320
Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn
325 330 335
Tyr Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met
340 345 350
Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu
355 360 365
Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe
370 375 380
His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu
385 390 395 400
Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu
405 410 415
Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln
420 425 430
Ser Ile Ile Ser Thr Leu Thr
435
<210> 104
<211> 5
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头变体34
<400> 104
Gly Gly Gly Gly Ser
1 5
<210> 105
<211> 371
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P34
<400> 105
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Gly Gly Gly Gly Ser Ala Pro
225 230 235 240
Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu
245 250 255
Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro
260 265 270
Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys Lys Ala
275 280 285
Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu
290 295 300
Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro
305 310 315 320
Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly
325 330 335
Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile
340 345 350
Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser
355 360 365
Thr Leu Thr
370
<210> 106
<211> 40
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 接头变体35
<400> 106
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 1015
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
202530
Gly Gly Ser Gly Gly Gly Gly Ser
3540
<210> 107
<211> 406
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> GI-101-P35
<400> 107
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Thr Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn Gly Gly Gly Gly Ser Gly Gly
225 230 235 240
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
245 250 255
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
260 265 270
Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu
275 280 285
His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr
290 295 300
Lys Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro
305 310 315 320
Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu
325 330 335
Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His
340 345 350
Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu
355 360 365
Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr
370 375 380
Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser
385 390 395 400
Ile Ile Ser Thr Leu Thr
405
<210> 108
<211> 233
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体36
<400> 108
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Glu Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Ala Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn
225 230
<210> 109
<211> 233
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体37
<400> 109
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Glu Asp Ala Phe Glu Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Ala Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn
225 230
<210> 110
<211> 233
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体38
<400> 110
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly Leu Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Asp Ile Leu Trp His Lys Glu Gly Lys Ile Val
505560
Leu Ala Met Arg Ser Gly Asp Thr Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Val Cys Val Val Arg Lys Tyr
100 105 110
Glu Asn Asp Thr Pro Val Leu Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Ala Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Ser Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn
225 230
<210> 111
<211> 233
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体39
<400> 111
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Gly Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Asp Ile Leu Trp His Lys Glu Gly Lys Ile Val
505560
Leu Ala Met Arg Ser Gly Asp Thr Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Ala Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Val Cys Val Val Arg Lys Tyr
100 105 110
Glu Asn Asp Thr Pro Val Leu Glu His Arg Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Ala Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys His
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn
225 230
<210> 112
<211> 233
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体40
<400> 112
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Gly Thr Leu Ser Cys Gly Leu Asn Val Ser Ala Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Ser Leu Ser Ile Ala Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Ala Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn
225 230
<210> 113
<211> 233
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体41
<400> 113
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Gly Thr Leu Ser Cys Gly Leu Asn Val Ser Ala Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Ser Leu Ser Ile Met Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Lys Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys Ala Asp Phe Pro Thr Pro Ser Ile Ser Asp Phe Glu Ile Pro
130 135 140
Thr Ser Asn Ile Arg Arg Ile Ile Cys Ser Ala Ser Gly Gly Phe Pro
145 150 155 160
Glu Pro His Leu Ser Trp Leu Glu Asn Gly Glu Glu Leu Asn Ala Ile
165 170 175
Asn Thr Thr Val Ser Gln Asp Pro Glu Thr Glu Leu Tyr Ala Val Ser
180 185 190
Ser Lys Leu Asp Phe Asn Met Thr Thr Asn His Ser Phe Met Cys Leu
195 200 205
Ile Lys Tyr Gly His Leu Arg Val Asn Gln Thr Phe Asn Trp Asn Thr
210 215 220
Thr Lys Gln Glu His Phe Pro Asp Asn
225 230
<210> 114
<211> 130
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> CD80变体42
<400> 114
Met Asp Ala Met Leu Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 1015
Ala Val Phe Val Ser Pro Ser His Ala Val Ile His Val Thr Lys Glu
202530
Val Lys Glu Val Ala Thr Leu Ser Cys Gly His Asn Val Ser Val Glu
354045
Glu Leu Ala Gln Thr Arg Ile Tyr Trp Gln Lys Glu Lys Lys Met Val
505560
Leu Thr Met Met Ser Gly Asp Met Asn Ile Trp Pro Glu Tyr Lys Asn
65707580
Arg Thr Ile Phe Asp Ile Thr Asn Asn Leu Ser Ile Val Ile Leu Ala
859095
Leu Arg Pro Ser Asp Glu Gly Thr Tyr Glu Cys Val Val Leu Lys Tyr
100 105 110
Glu Glu Asp Ala Phe Lys Arg Glu His Leu Ala Glu Val Thr Leu Ser
115 120 125
Val Lys
130
<210> 115
<211> 133
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> hIL2v_3M
<400> 115
Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His
1 5 1015
Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys
202530
Asn Pro Lys Leu Thr Ala Met Leu Thr Ala Lys Phe Tyr Met Pro Lys
354045
Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Arg Glu Leu Lys
505560
Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu
65707580
Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu
859095
Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala
100 105 110
Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile
115 120 125
Ile Ser Thr Leu Thr
130
- 包含IL-2蛋白和CD80蛋白的融合蛋白及其用途
- 包含IL-2蛋白和CD80蛋白的融合蛋白制剂