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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Coevolution of TCR-MHC interactions: Conserved MHC tertiary structure is not sufficient for interactions with the TCR
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Coevolution of TCR-MHC interactions: Conserved MHC tertiary structure is not sufficient for interactions with the TCR

机译：TCR-MHC相互作用的共同进化：保守的MHC三级结构不足以与TCR相互作用

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The specificity for self-MHC that is necessary for T cell function is a consequence of intrathymic selection during which T cell antigen receptors (TCRs) expressed by immature thymocytes are tested for their affinity for self-peptide:self-MHC. The germ-line-encoded segments of the TCR, however, are believed to have an innate specificity for structural features of MHC molecules. We directly tested this hypothesis by generating a transgenic mouse system in which the protein HLA-DM is expressed at the surface of thymic cortical epithelial cells in the absence of classical MHC molecules. The specialized intracellular function of HLA-DM has removed this MHC class II-like protein from the evolutionary forces that have been hypothesized to shape TCR-MHC interactions. Our study shows that a structural mimic of MHC class II is not sufficient to appropriately interact with the TCRs expressed by developing thymocytes. This result emphasizes the unique complementarity of TCR-MHC interactions that are maintained by the evolutionary pressures dictated by positive selection.
机译：T细胞功能所必需的自身MHC特异性是胸腺内选择的结果，在胸腺内选择测试了未成熟胸腺细胞表达的T细胞抗原受体（TCR）对自身肽：自身MHC的亲和力。然而，据信TCR的种系编码片段对MHC分子的结构特征具有先天特异性。我们通过产生一种转基因小鼠系统直接测试了这一假设，其中在经典MHC分子不存在的情况下，蛋白质HLA-DM在胸腺皮质上皮细胞表面表达。 HLA-DM的特殊细胞内功能已经从进化力中去除了这种MHC II类蛋白，该蛋白被认为可以塑造TCR-MHC相互作用。我们的研究表明，II类MHC的结构模拟不足以与发育中的胸腺细胞表达的TCR适当相互作用。该结果强调了TCR-MHC相互作用的独特互补性，该互补性由阳性选择所决定的进化压力所维持。

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