Howard Hughes Medical Institute, Denver, United States.
Department of Biomedical Research, National Jewish Health, Denver, United States.
Elife. 2017 Nov 17;6:e30918. doi: 10.7554/eLife.30918.
Mature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded portions of CDR3 of the T cell receptor α chain. Thus, in addition to determining specificity for antigen, the non germline encoded elements of T cell receptors may help the proteins cope with the extremely polymorphic nature of major histocompatibility complex products within the species.
成熟的 T 细胞带有 αβ T 细胞受体，与它们在胸腺发育过程中接触到的主要组织相容性复合体蛋白（MHC）等位基因结合的外来抗原发生反应，这一现象被称为阳性选择。阳性选择的结构基础长期以来一直存在争议。在这里，我们使用表达两种不同 T 细胞受体 β 链和各种 MHC 等位基因的小鼠，表明阳性选择诱导的 T 细胞受体对 MHC 的偏倚受到 T 细胞受体 α 和 β 链的胚系编码元件的影响，并且令人惊讶的是，还受到 T 细胞受体 α 链 CDR3 的非胚系编码部分的显著影响。因此，除了决定抗原特异性外，T 细胞受体的非胚系编码元件可能有助于蛋白质应对同种主要组织相容性复合体产物的极度多态性。
