Li Xia, Li Ru, Zhang Cui-hua, Li Zhan-guo
Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing 100044, China.
Zhonghua Yi Xue Za Zhi. 2005 Jun 29;85(24):1679-82.
To study the inhibitory role of altered HA308 - 317 peptides in T cell responses in patients with rheumatoid arthritis (RA).
Peripheral blood mononuclear cells (PBMC) were obtained from 27 HLA-DRB1 positive RA patients. T cell responses to altered HA308-317 peptides were examined by using (3)H incorporation assay. The level of IL-2 and IFNgamma in the supernatants was identified by an enzyme-linked immunosorbent assay. The CD69 expression on T cell surface was studied by using flow cytometry.
Compared to wild type CII263 - 272 or HA308 - 317, altered HA308 - 317 peptides failed to stimulate T cell proliferation (P < 0.05) and production of IL-2 as well as IFNgamma and resulted in lower expression of CD69 in RA patients (P < 0.05). SI values for T cell coincubated with altered HA308 - 317 peptides and CII263 - 272 or wild type HA308 - 317 were significantly lower than coincubated with CII263 - 272 and wild type HA308 - 317 alone (P < 0.05).
Substitution of TCR-binding residue of HA308 - 317 yielded weak or non-T-cell stimulating peptides, which might be potentially effective in blocking abnormal T cell responses in RA.
研究改变的HA308 - 317肽对类风湿关节炎(RA)患者T细胞反应的抑制作用。
从27例HLA - DRB1阳性的RA患者中获取外周血单个核细胞(PBMC)。采用³H掺入法检测T细胞对改变的HA308 - 317肽的反应。通过酶联免疫吸附测定法鉴定上清液中白细胞介素 - 2(IL - 2)和γ干扰素(IFNγ)的水平。利用流式细胞术研究T细胞表面CD69的表达。
与野生型CII263 - 272或HA308 - 317相比,改变的HA308 - 317肽未能刺激T细胞增殖(P < 0.05)以及IL - 2和IFNγ的产生,并导致RA患者中CD69的表达降低(P < 0.05)。与改变的HA308 - 317肽以及CII263 - 272或野生型HA308 - 317共同孵育的T细胞的刺激指数(SI)显著低于仅与CII263 - 272和野生型HA308 - 317共同孵育的情况(P < 0.05)。
HA308 - 317的T细胞受体结合残基的取代产生了弱的或无T细胞刺激作用的肽,这可能对阻断RA中异常的T细胞反应具有潜在效果。