The molecular basis of TCR germline bias for MHC is surprisingly simple.
The molecular basis of TCR germline bias for MHC is surprisingly simple.
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最近的“概念验证”结构结果表明，在具有共同可变片段和MHC同种异型的复合物中，特异性TCR-MHC界面接触的保守性，阐明了T细胞受体（TCR）对主要组织相容性复合物（MHC）的种系偏好的难以捉摸的病因。我们认为，每个TCR可变区基因产物通过共同进化产生的结构编码识别基序的“菜单”参与每种类型的MHC。在胸腺选择和外周监测过程中对MHC限制性T细胞识别的要求使得这种编码识别系统的存在成为必要。考虑到这些发现，对TCR-肽-MHC结构数据库的重新考虑表明，答案不仅沿着存在，而且它们可以通过物理化学的第一原理来预测。
The elusive etiology of germline bias of the T cell receptor (TCR) for major histocompatibility complex (MHC) has been clarified by recent ‘proof-of-concept’ structural results demonstrating the conservation of specific TCR-MHC interfacial contacts in complexes bearing common variable segments and MHC allotypes. We suggest that each TCR variable-region gene product engages each type of MHC through a ‘menu’ of structurally coded recognition motifs that have arisen through coevolution. The requirement for MHC-restricted T cell recognition during thymic selection and peripheral surveillance has necessitated the existence of such a coded recognition system. Given these findings, a reconsideration of the TCR–peptide-MHC structural database shows that not only have the answers been there all along but also they were predictable by the first principles of physical chemistry.
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