流感病毒血凝素衍生肽对T细胞活化抑制作用的研究  

Inhibition on T cell activation by influenza virus haemagglutinin-derived peptides

作　　者：李霞[1] 李茹 张翠华[1] 李博[2] 栗占国[1] 

机构地区：[1]北京大学人民医院风湿免疫科,100044 [2]北京大学物理化学学院分子与结构生物实验室

出　　处：《中华风湿病学杂志》2005年第6期325-328,i001,共5页Chinese Journal of Rheumatology

基　　金：国家自然科学基金资助项目(30271223)

摘　　要：目的研究人类白细胞抗原(HLA)-DRB1结合性流感病毒血凝素(HA)308-317变构肽在HLA-DR4限制性T细胞激活中的作用。方法采用固相法合成HA308-317原型肽及其变构肽。通过计算机模拟及流式细胞术分析HA308-317原型肽及其变构肽与HLA-DR4分子的结合作用;并检测这些多肽对T细胞激活信号CD69表达和白细胞介素(IL)-2分泌的影响及对T细胞增殖的抑制作用。结果HA308-317变构肽能结合细胞表面HLA-DR4分子,对T细胞激活信号CD69表达和IL-2分泌无明显影响,并能抑制HA308-317原型肽诱导的T细胞活化。结论替换HA308-317多肽中识别T细胞受体(TCR)的氨基酸残基形成的HA变构肽可与HLA-DR4分子结合,而且可抑制其原型肽诱导的T细胞活化。Objective To evaluate the impact of HLA-DR4 specific influenza virus hemagglutinin (HA) 308-317 peptide and its altered peptide ligands on T cell activation. Methods HA308-317 peptide and its altered peptide ligands were synthesized using solid-phase techniques. The affinity of wild type HA308-317 and its altered peptide ligands for HLA-DR4 were analyzed by computer modeling. The competitive binding of altered HA308-317 peptides and wild type HA308-317 for HLA-DR4 molecules were examined using flow cytometry. The interleukin (IL)-2 level in the supernatants was evaluated by ELISA. The expression of CD69 on T cell surface was studied using flow cytometry. The suppressive effects of altered HA308-317 peptides on T cell proliferation was determined by measuring IL-2 production. Results Altered HA308-317 peptides were able to bind to HLA-DR4 molecules and competed with wild type HA308-317. Compared to cells stimulated by wild type HA308-317, altered HA308-317 peptides did not stimulate significant IL-2 production and CD69 expression. Further, altered HA308-317 peptides did not inhibite T cell activation and IL-2 production induced by wild type HA308-317 peptide. Conclusion Altered HA308-317 peptides with substitutions of T cell receptor-binding residues can inhibite T cell activation induced by wild type HA308-317. Altered HA308-317 peptides may be potentially useful in inhibiting HLA-DRB1 specific T cell-mediated autoimmune responses.

关 键 词：流感病毒血凝素 T细胞活化 抑制作用 HLA-DR4 T细胞激活信号 衍生肽 人类白细胞抗原 CD69 流式细胞术 计算机模拟 T细胞增殖 白细胞介素 氨基酸残基 T细胞受体 变构肽 结合作用 IL-2 细胞表面 原型 限制性 结合性 固相法 

分 类 号：R392.1[医药卫生—免疫学]