Chilvers M M, Wordsworth P, Stubbs A, Gao X M
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, United Kingdom.
J Immunol. 1998 Apr 15;160(8):3737-42.
We have recently demonstrated that homocysteine can modify HLA class I Ags and induce homocysteine-specific CTL (Hom-CTL) responses in humans. Here, we have investigated TCR usage by Hom-CTL from five patients with ankylosing spondylitis or reactive arthritis. TCR of HLA-A68-restricted Hom-CTL from two unrelated donors share the same TCR Valpha, Vbeta, and Jbeta gene segments (AV4, BV23, and BJ2S1, respectively) with similar third complementarity determining regions (CDR3) of the beta-chains. Interestingly, the Va and Vbeta gene segments employed by an HLA-B27-restricted Hom-CTL clone are also closely related to AV4 and BV23, indicating strong selection pressure for AV4, BV23, and related gene products in the homocysteine-specific TCR. An arginine or lysine residue frequently appeared at position alpha93 in the CDR3 of the TCR alpha-chains from Hom-CTL restricted by HLA-A68 or -B8. This may suggest a potential salt bridge between the carboxyl group of homocysteine and specific TCR. TCR usage by HLA-B27-restricted Hom-CTL from unrelated individuals appears to be less conserved, although two T cell clones from one individual rearranged the same V gene segments with identical lengths of CDR3. Implications of these data for the molecular mechanisms for homocysteine modification of HLA Ags are also discussed.
我们最近证实，同型半胱氨酸可修饰人类的HLA I类抗原，并诱导同型半胱氨酸特异性CTL（Hom-CTL）应答。在此，我们研究了5例强直性脊柱炎或反应性关节炎患者的Hom-CTL的TCR使用情况。来自两名无关供体的HLA-A68限制性Hom-CTL的TCR共享相同的TCR Vα、Vβ和Jβ基因片段（分别为AV4、BV23和BJ2S1），其β链的第三个互补决定区（CDR3）相似。有趣的是，一个HLA-B27限制性Hom-CTL克隆所使用的Vα和Vβ基因片段也与AV4和BV23密切相关，这表明在同型半胱氨酸特异性TCR中，AV4、BV23及相关基因产物受到了强烈的选择压力。在受HLA-A68或-B8限制的Hom-CTL的TCRα链的CDR3中，α93位经常出现精氨酸或赖氨酸残基。这可能提示同型半胱氨酸的羧基与特定TCR之间存在潜在的盐桥。来自无关个体的HLA-B27限制性Hom-CTL的TCR使用情况似乎保守性较差，尽管来自一个个体的两个T细胞克隆重排了相同的V基因片段，且CDR3长度相同。本文还讨论了这些数据对HLA抗原同型半胱氨酸修饰分子机制的意义。
