Li X, Li R, Li Z
Department of Rheumatology and Immunology, People's Hospital, Beijing University, Beijing, China.
Clin Exp Rheumatol. 2006 Mar-Apr;24(2):148-54.
To investigate whether influenza virus haemagglutinin (HA)-derived altered peptide ligands (APLs) could abrogate T-cell responses to wild type HA308-317 or type II collagen (CII) 263-272 peptides and explore the potential inhibitory effects of the altered HA308-317 peptides on T-cell activation in rheumatoid arthritis (RA).
Altered HA308-317 peptides containing substitutions of T-cell receptor (TCR)-contact residues were synthesized. Peripheral blood mononuclear cells (PBMC) were obtained from 27 HLA-DR4/1-positive RA patients. Impact of the altered HA308-317 peptides on T-cell responses and the inhibitory effects on T-cell activation were determined by using PBMC from RA.
The results showed that the altered HA308-317 peptides could bind to HLA-DR4/1 on cell surface and had no effects on T-cell proliferation and CD25 expression. Moreover, all the altered HA308-317 peptides inhibited T-cell proliferative responses to wild type HA308-317 or CII263-272. In addition, Th1 type cytokine profile was found when PBMC were cultured with wild type HA308-317 or CII263-272, but not the altered HA 308-317 peptides.
It is suggested that altered HA308-317 peptides bind to the RA-associated HLA-DR4/1 with no stimulating effects on T cells and might be potentially important in inhibition of T-cell activation in RA.
研究流感病毒血凝素（HA）衍生的修饰肽配体（APL）是否能够消除T细胞对野生型HA308 - 317或II型胶原蛋白（CII）263 - 272肽的反应，并探讨修饰后的HA308 - 317肽对类风湿性关节炎（RA）中T细胞活化的潜在抑制作用。
合成含有T细胞受体（TCR）接触残基替代的修饰HA308 - 317肽。从27名HLA - DR4/1阳性的RA患者中获取外周血单个核细胞（PBMC）。使用来自RA患者的PBMC确定修饰后的HA308 - 317肽对T细胞反应及T细胞活化的抑制作用。
结果显示，修饰后的HA308 - 317肽可与细胞表面的HLA - DR4/1结合，且对T细胞增殖和CD25表达无影响。此外所有修饰后的HA308 - 317肽均抑制T细胞对野生型HA308 - 317或CII263 - 272的增殖反应。另外，当PBMC与野生型HA308 - 317或CII263 - 272共培养时可发现Th1型细胞因子谱，但与修饰后的HA308 - 317肽共培养时未发现。
提示修饰后的HA308 - 317肽可与RA相关的HLA - DR4/1结合，对T细胞无刺激作用，可能在抑制RA中T细胞活化方面具有潜在重要意义。
