利用II型胶原变构肽抑制类风湿关节炎患者T细胞活化的研究  

The inhibitory effect of the altered collagen II peptide on T cell activation in patients with rheumatoid arthritis

作　　者：李茹 李霞[2] 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 [2]大连大学医学院,大连110066

出　　处：《现代免疫学》2006年第3期217-221,共5页Current Immunology

基　　金：国家自然科学基金资助项目(30271223);北京市自然科学基金资助项目(7041005)

摘　　要：为了研究II型胶原(CII)变构肽对类风湿性关节炎(RA)患者外周血T细胞激活的抑制作用,以固相法合成CII263-272原型肽及3条变构肽,计算机模拟分析变构肽与HLA-DR4分子的结合能力3。H掺入法检测61例RA患者外周血单个核细胞对CII263-272原型肽及变构肽的T细胞增殖反应。ELISA法检测CII263-272原型肽及变构肽刺激下外周血T细胞IL-2及IFN-γ的分泌。竞争抑制试验观察CII变构肽对原型肽介导T细胞激活的抑制作用。计算机模拟结果发现,CII263-272原型肽可与HLA-DR4分子结合,在此基础上替换TCR结合位点267位谷氨酰胺、270位赖氨酸和271或265位甘氨酸为丙氨酸,不影响该多肽与HLA-DR4分子的结合能力。CII变构肽在RA患者外周血T细胞具增殖中有明显低反应性,下调IL-2和IFN-γ的产生,并且可特异性抑制CII原型肽诱导的T细胞活化(P<0.05或P<0.01)。以上结果提示,替换CII263-272多肽中与T细胞受体结合的氨基酸形成的CII变构肽可抑制RA患者外周血T细胞活化,可能在本病的免疫治疗中有重要意义。To observe the inhibitory effect of the altered collagen Ⅱ peptide（CII263 272 peptides） on T cell activation in patients with rheumatoid arthritis （RA）, three altered CII263-272 peptides（APL） were synthesized in our laboratory and the interaction of APL with HLA-DR4 molecule was analysed by means of compeuter modeling. Peripheral blood mononuclear cells （PBMC）were obtained from 61 patients with RA for investigation, in which the T cell responses to the original CII263-272 peptide and altered APL and the capacity of APL to inhibit the induced T cell activation were examined by using ^3H-incorporation assay, while the levels of IL-2 and IFN-γ in the supernatants of the cultured cell population were assayed by ELISA. The results showed that all these 3 APL could hind with HLA-DR4 molecule, but it showed no effect on the T cell activation in patients with RA. Also, it could down-regulate the secretion of IL-2 and IFN-γ and inhibit the CII263-272 peptide-induced T cell activation in a dose dependent manner. These resuhs suggest that substitution of the TCR-binding residue of the CII263-272 peptides yields an altered ligand which might be potential for the immuno-suppression in patients with RA.

关 键 词：类风湿关节炎 Ⅱ型胶原 T细胞活化 

分 类 号：R392.12[医药卫生—免疫学]