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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

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【作者】 李茹李霞栗占国

【Author】 LI Ru,LI Xia,LI Zhan-guo(Department of Rheumatology and Immunology,People’s Hospital,Peking University,Beijing 100044,China)

【机构】 北京大学人民医院风湿免疫科大连大学医学院北京大学人民医院风湿免疫科 北京100044大连110066北京100044

【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。

【Abstract】 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 bind 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 results 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.

【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)
  • 【文献出处】 现代免疫学 ,Current Immunology , 编辑部邮箱 ,2006年03期
  • 【分类号】R593.22
  • 【被引频次】3
  • 【下载频次】182
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