HA308-317变构肽对HLA-DR4特异性T细胞活化的抑制作用  

Altered HA308-317 peptides inhibit HLA-DR4 specific T cell response

作　　者：李霞[1] 周强[1] 李茹 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4期299-303,307,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金 (3 9970 697);国家杰出青年基金(3 0 0 2 5 0 40 )资助项目

摘　　要：目的:研究流感病毒血凝素(HA) 30 8- 317变构肽对人类白细胞抗原(HLA) - DR4限制性Ⅱ型胶原(CII)特异性T细胞激活的抑制作用。方法:采用固相法合成3条HA30 8 317变构肽。流式细胞术分析HA30 8- 317变构肽与细胞表面HLA- DR4分子的结合作用;3H掺入法检测HA30 8- 317变构肽对CII2 6 3 2 72介导T细胞增殖的抑制作用;ELISA法检测上清液中IL- 2的水平;流式细胞术分析细胞表面CD2 5和CD6 9的表达情况。结果:HA30 8- 317变构肽能竞争性地抑制CII2 6 3 2 72与细胞表面HLA DR4分子的结合;HA30 8 317变构肽抑制了CII2 6 3 2 72诱导的T细胞增殖和IL 2的分泌;与CII2 6 3 2 72相比,HA30 8 -317变构肽诱导T细胞表面CD2 5或CD6 9的表达减弱。结论:替换HA30 8 317多肽中与T细胞受体结合的氨基酸形成的HA变构肽不改变其与HLA- DR4的结合能力,但它们抑制T细胞的活化。在T细胞介导的自身免疫病中,变构肽的应用可能是一种新的治疗策略。Objective:To evaluate the inhibitory effect of altered HA308-317 peptides on HLA-DR4 restricted CII specific T cell response.Methods:Three altered HA308-317 peptides and CII263-272 were synthesized using solid-phase techniques. The binding of altered HA308-317 peptides for HLA-DR4 molecules was assayed using flow cytometry. The suppressive effect of altered HA308-317 peptides on CII-mediated T cell proliferation was determined using 3H incorporation assay. The level of IL-2 in the supernatants was identified by ELISA. The expression of CD25 and CD69 on T cell surface were studied using flow cytometry.Results:The altered HA308-317 peptides were able to bind to HLA-DR4 molecules and competed with CII263-272. Altered HA308-317 peptides inhibited T cell proliferation and IL-2 production induced by CII263-272( P <0.05).The CD25 and CD69 expression on cells stimulated by the altered HA308-317 was much lower, compared to cells stimulated by CII263-272.Conclusion:The altered HA308-317 peptides with the substitutions of T cell receptor residues inhibited CII-induced T cell activation. It may suggest a new therapeutic strategy in T cell-mediated autoimmune diseases.

关 键 词：HLA-DR4 变构肽 流感病毒血凝素 Ⅱ型胶原 T细胞激活 

分 类 号：R392.12[医药卫生—免疫学]