HLA-DRB1结合性变构肽对T细胞活化的竞争性抑制作用  

The competitive inhibitory effects of HLA-DRB1-binding peptide on T cell activation

作　　者：程永静[1] 周强[1] 栗占国[1] 

机构地区：[1]北京大学人民医院风湿免疫科,北京100044

出　　处：《中国免疫学杂志》2005年第10期731-734,738,共5页Chinese Journal of Immunology

基　　金：国家杰出青年基金(批准号:301025040);北京大学985基金资助项目

摘　　要：目的:研究去除T细胞受体(TCR)识别表位的HLA-DRB1结合性Ⅱ型胶原(CⅡ)变构肽对T细胞活化的抑制作用.方法:将人CⅡ的抗原性片段(CⅡ263-272)中与T细胞识别有关的268～270位氨基酸分别用丙氨酸和甘氨酸替换,形成CⅡ变构肽S268-270,并将该多肽与表达HLA-DR1的抗原呈递细胞(APC)及抗原性原型CⅡ263-272多肽共同孵育,研究变构肽S268-270在竞争性抑制CⅡ263-272与HLA-DR1分子结合中的作用;利用HLA-DR1转基因APC及其特异性T细胞,研究S268-270对抗原性CⅡ263-272及流感病毒血凝素(HA)306-318诱导的T细胞活化的抑制作用.结果:CⅡ变构肽S268-270可结合APC表面的HLA-DR1分子,并可抑制CⅡ263-272及HA306-318两种不同抗原诱导的HLA-DR1限制性T细胞活化.结论:替换CⅡ263-272中与TCR识别有关的氨基酸所形成的CⅡ变构肽S268-270可与APC表面的HLA-DR1分子结合,并可抑制HLA-DR1结合性抗原肽CⅡ263-272及HA306-318诱导的T细胞活化.CⅡ变构肽S268-270可能对类风湿关节炎患者的HLA-DR1限制性T细胞异常活化具有抑制作用.Objective;To evaluate the impact of altered collagen Ⅱ （C Ⅱ ） peptide（S268-270） on T cell activation. Methods： Altered CⅡ 263-272 with G268,P269 and K270 consecutively substitution with A or G were synthesized using solid phase various concentrations were added to HLA-DR1 transfected APC. Expression of FTTC stainning was analyzed by fluorescence-activated cell sorting, and the binding of altered C Ⅱ peptide to HLA-DR1 molecule on cell membrane was evaluated. Irridiated HLA-DR1 expressing APC was incubated with C Ⅱ 263-272 or hemagglufinin（HA）306-318 and altered C Ⅱ peptides at various concentrations for 2 hours before T cells（3.19） were added. Supematant was harvested and then added to IL-2 dependent CTLL cell. The cell proliferation was examined by methotetrazolium（MTT） method. Results： The altered C Ⅱ peptide and wild type of C Ⅱ 263-272 were able to competitively bind to HLA-DR1 molecule expressed on cell membrane of transfected APC. C Ⅱ or HA induced T cell activation was significantly inhibited by the altered peptide S268-270. Conclusion： Altered C Ⅱ 263-272 with G268,P269 and K270 consecutively substitutions with A or G inhibited C Ⅱ 263-272 and HA306-318 induced T cell activation through competitively binding to HLA-DR1, suggesting a new approach in inhibition of T cell activation in RA.

关 键 词：Ⅱ型胶原 HLA-DR1 T细胞受体 多肽 类风湿关节炎 

分 类 号：R392[医药卫生—免疫学]