人类白细胞抗原-DR1特异性流感病毒血凝素多肽对T细胞激活抑制作用的研究

Inhibitory effect of HLA-DR1-specific influenza virus hemagglutitin peptide on T cell activation

目的研究流感病毒血凝素(HA)306-318多肽在人类白细胞抗原(HLA)-DR1限制性T细胞激活中的作用,以及HA306-318变构肽对T细胞活化的影响,探讨利用HA306-318变构肽抑制类风湿关节炎(RA)患者T细胞活化的可行性。方法利用HLA-DR1转基因细胞株检测去除T细胞受体(TCR)结合位点的HA306-318变构肽与HLA-DR1分子的结合。以HLA-DR1限制性抗原递呈系统,四甲基偶氮唑蓝(MTT)法检测HA306-318及其变构肽诱导T细胞活化的作用,以及该变构肽对T细胞活化的抑制作用。结果HA306-318原型肽可以活化HLA-DR1限制性T细胞,可诱导细胞增生及分泌白细胞介素(IL)-2;HA306-318变构肽可与HLA-DR1分子结合,无T细胞激活能力,并可有效抑制HA306-318原型肽以及Ⅱ型胶原(CⅡ)263-272多肽诱导的T细胞活化。结论HA306-318多肽可以介导HLA-DR1特异性T细胞激活,HA306-318变构肽作为HLA-DR1特异性非T细胞激活肽,可以抑制HA306-318以及CⅡ263-272抗原肽诱导的T细胞活化。

Objective To evaluate the impact of influenza virus hemagglutitin (HA) 306-318 peptide on T cell activation and to investigate the inhibitory effect of the altered HA306-318 peptide on T cell proliferation. Methods HA306-318 peptide and its mutant containing amino acid substitutions were synthesized. They were used in T cell activation assay using HLA-DR1 transfected cells. Responses were determined by MTT proliferation assays. The HA mutant without stimulating effect on T cells was then examined by inhibiting HLA-DR1-restricted T cell activation. Results It was demonstrated in this study that the altered HA306-318 peptide bound to HLA-DR1 molecule on L57.23 cells transfected with HLA-DR1 cDNA, but not on the control cells. The altered HA306-318 peptide had no stimulating effect on T cells compared with the wild type HA306-318 which induced T cell proliferation. It was shown that the altered HA peptide inhibited T cell activation mediated by wild type HA306-318 as well as by CⅡ263-272 which was the specific T cell antigen. Conclusions This study suggests that HA306-318 peptide is antigenic and can induce responses in HLA-DR1 specific T cells. Altered HA306-318 peptide is hyporesponsive in T cell activation with inhibitory effect on antigen-driven T cell responses, and it is potentially a therapeutic agent in rheumatoid arthritis.