Integrated Department of Immunology, National Jewish Health and University of Colorado School of Medicine, Denver, CO 80206, USA.
Immunity. 2011 Oct 28;35(4):526-35. doi: 10.1016/j.immuni.2011.09.005. Epub 2011 Sep 29.
αβ T cell receptors (TCRs) bind specifically to foreign antigens presented by major histocompatibility complex proteins (MHC) or MHC-like molecules. Accumulating evidence indicates that the germline-encoded TCR segments have features that promote binding to MHC and MHC-like molecules, suggesting coevolution between TCR and MHC molecules. Here, we assess directly the evolutionary conservation of αβ TCR specificity for MHC. Sequence comparisons showed that some Vβs from distantly related jawed vertebrates share amino acids in their complementarity determining region 2 (CDR2). Chimeric TCRs containing amphibian, bony fish, or cartilaginous fish Vβs can recognize antigens presented by mouse MHC class II and CD1d (an MHC-like protein), and this recognition is dependent upon the shared CDR2 amino acids. These results indicate that features of the TCR that control specificity for MHC and MHC-like molecules were selected early in evolution and maintained between species that last shared a common ancestor more than 400 million years ago.
αβ T 细胞受体 (TCR) 特异性结合主要组织相容性复合体蛋白 (MHC) 或 MHC 样分子呈递的外来抗原。越来越多的证据表明，胚系编码的 TCR 片段具有促进与 MHC 和 MHC 样分子结合的特征，提示 TCR 和 MHC 分子之间存在共同进化。在这里，我们直接评估 αβ TCR 对 MHC 的特异性的进化保守性。序列比较表明，来自远缘有颌脊椎动物的一些 Vβ 在其互补决定区 2 (CDR2) 中具有相同的氨基酸。包含两栖类、硬骨鱼类或软骨鱼类 Vβ 的嵌合 TCR 可以识别由小鼠 MHC Ⅱ类和 CD1d（一种 MHC 样蛋白）呈递的抗原，这种识别依赖于共享的 CDR2 氨基酸。这些结果表明，控制 TCR 对 MHC 和 MHC 样分子特异性的特征是在进化早期被选择的，并在 4 亿多年前最后一次拥有共同祖先的物种之间得以维持。
