HA308-317变构肽对HLA-DR4特异性T细胞活化的抑制作用

目的：研究流感病毒血凝素(HA)308-317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HA308-317变构肽。流式细胞术分析HA308-317变构肽与细胞表面HLA-DR4分子的结合作用；^3H掺人法检测HA308-317变构肽对CII263-272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CD25和CD69的表达情况。结果：HA308-317变构肽能竞争性地抑制CII263-272与细胞表面HLA-DR4分子的结合；HA308-317变构肽抑制了CU263-272诱导的T细胞增殖和IL-2的分泌；与CII263-272相比，HA308-317变构肽诱导T细胞表面CD25或CD69的表达减弱。结论：替换HA308-317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。

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

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.