Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'
Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'
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DOI：
10.1038/ni1502
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发表时间：
2007-09-01
影响因子：
30.5
通讯作者：
Garcia, K. Christopher
中科院分区：
文献类型：
--
作者：
Feng, Dan;Bond, Christopher J.;Garcia, K. Christopher
所有与肽-主要组织相容性复合物（pMHC）分子结合的T细胞受体复合物（tcr）都具有固定的结合“极性”，尽管TCR-pMHC对接角度存在很大差异。然而，现有的TCR-pMHC晶体结构未能显示出广泛保守的成对相互作用基序。在这里，我们确定了由可变β链8.2 （V(beta)8.2）编码的两个tcr的晶体结构，每个tcr都与MHC II类分子I-A(u)结合，并对V- α和V- β与I-A(u)的接触进行了能量映射。与先前已知的两个含V(β)8.2的TCR-MHC配合物结构一起，我们发现了四个TCR-I-A配合物，它们的V- β环和I-A α -螺旋之间具有结构上可重叠的相互作用。对TCR-MHC基因库的狭窄“切片”的检查表明，这可能是许多种系衍生的TCR-MHC相互作用“密码子”之一。
All complexes of T cell receptors (TCRs) bound to peptide-major histocompatibility complex (pMHC) molecules assume a stereotyped binding 'polarity', despite wide variations in TCR-pMHC docking angles. However, existing TCR-pMHC crystal structures have failed to show broadly conserved pairwise interaction motifs. Here we determined the crystal structures of two TCRs encoded by the variable beta-chain 8.2 (V(beta)8.2), each bound to the MHC class II molecule I-A(u), and did energetic mapping of V-alpha and V-beta contacts with I-A(u). Together with two previously solved structures of V(beta)8.2-containing TCR-MHC complexes, we found four TCR-I-A complexes with structurally superimposable interactions between the V-beta loops and the I-A alpha-helix. This examination of a narrow 'slice' of the TCR-MHC repertoire demonstrates what is probably one of many germline-derived TCR-MHC interaction 'codons'.