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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 study the inhibitory effect of HLA-DRB1-binding type Ⅱ collagen (CⅡ) allosteric peptides on the activation of T cells by removing T cell receptor (TCR) recognition epitopes. METHODS: Amino acid residues 268-270 of the antigenic fragment (CⅡ263-272) of human CⅡ were replaced by alanine and glycine respectively to form CⅡ allosteric peptide S268-270. HLA-DR1 antigen presenting cells (APC) and antigenic prototype CⅡ263-272 polypeptide co-incubated to study the role of allosteric peptide S268-270 in the competitive inhibition of C Ⅱ 263-272 and HLA-DR1 binding molecules; the use of HLA-DR1 transgene APC and its specific T cells to study the inhibitory effect of S268-270 on T cell activation induced by antigenic CII263-272 and influenza virus hemagglutinin (HA) 306-318. Results: The CⅡ allosteric peptide S268-270 could bind to HLA-DR1 on the surface of APC and inhibit the activation of HLA-DR1-restricted T cells induced by two different antigens, CⅡ263-272 and HA306-318. CONCLUSION: The CⅡ allosteric peptide S268-270 formed by replacing the amino acids related to TCR recognition in CⅡ263-272 binds to the HLA-DR1 molecule on the APC surface and inhibits HLA-DR1-binding antigenic peptides CⅡ263-272 and HA306- 318-induced T cell activation. CⅡ allosteric peptide S268-270 may inhibit the abnormal activation of HLA-DR1-restricted T cells in patients with rheumatoid arthritis.