1类主要组织相容性复合体的结构模式-限制nonamer肽与T细胞受体的结合

R. T, Jeremy C. Smith
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引用次数: 3

摘要

αβ T细胞受体(TCR)序列和结构的惊人多样性使得在分子水平上分析T细胞免疫原性的特异性和敏感性变得复杂。目前,tcr和多肽之间的三元复合物有许多三维(3D)结构:主要组织相容性复合物(pMHC)。在这里,为了收集分子水平的见解,我们分析了与人类I类氨基肽- mhc复合物结合的tcr的结构。发现肽位4-8的残基对TCR结合特别重要。约90%的tcr氢键与MHC等位基因HLA‐A2所呈现的4位和8位的一个或两个肽残基结合,而对于其他MHC等位基因所呈现的肽,这一比例仍为79%。残基8位于先前鉴定的中心肽区域之外,对于TCR识别I类MHC - present nonamer肽至关重要。相互作用的统计也揭示了对TCR结合重要的MHC残基。目前的分析将有助于TCR:pMHC复合物的结构建模,并对基于肽的疫苗和基于T细胞的免疫疗法的合理设计具有指导意义。
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Structural patterns in class 1 major histocompatibility complex‐restricted nonamer peptide binding to T‐cell receptors
The startling diversity in αβ T‐cell receptor (TCR) sequences and structures complicates molecular‐level analyses of the specificity and sensitivity determining T‐cell immunogenicity. A number of three‐dimensional (3D) structures are now available of ternary complexes between TCRs and peptides: major histocompatibility complexes (pMHC). Here, to glean molecular‐level insights we analyze structures of TCRs bound to human class I nonamer peptide–MHC complexes. Residues at peptide positions 4–8 are found to be particularly important for TCR binding. About 90% of the TCRs hydrogen bond with one or both of the peptide residues at positions 4 and 8 presented by MHC allele HLA‐A2, and this number is still ~79% for peptides presented by other MHC alleles. Residue 8, which lies outside the previously‐identified central peptide region, is crucial for TCR recognition of class I MHC‐presented nonamer peptides. The statistics of the interactions also sheds light on the MHC residues important for TCR binding. The present analysis will aid in the structural modeling of TCR:pMHC complexes and has implications for the rational design of peptide‐based vaccines and T‐cell‐based immunotherapies.
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