How a single T cell receptor recognizes both self and foreign MHC
How a single T cell receptor recognizes both self and foreign MHC
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DOI：
10.1016/j.cell.2007.01.048
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发表时间：
2007-04-06
期刊：
影响因子：
64.5
通讯作者：
Garcia, K. Christopher
中科院分区：
文献类型：
--
作者：
Colf, Leremy A.;Bankovich, Alexander J.;Garcia, K. Christopher
α β T细胞受体（TCR）可以与自身和外来主要组织相容性复合体（MHC）蛋白交叉反应，这是一种被称为同种异体反应性的神秘现象。在这里，我们呈现了与其外源配体H-2L（d）-QL 9复合的2C TCR的2.35埃结构。令人惊讶的是，我们发现与其识别自身配体H-2K（B）-dEV 8的方式相比，该TCR利用不同的策略来接合外源pMHC。2C以独特的成对接触接合L-d和K-b上的共享和多态残基以及不相关的QL 9和dEV 8肽抗原，导致与L-d-QL 9复合物的更大的结构互补性。在与H-2L（d）-QL 9结合的工程化高亲和力2C TCR变体的结构中，尽管TCR-CDR 3 α与肽发生了修饰，但“野生型”TCR-MHC结合方向仍然存在。因此，单个TCR通过不同的机制识别两种全局相似但不同的配体，表明受体-配体交叉反应性可以在不存在分子模拟的情况下发生。
alpha beta T cell receptors (TCRs) can crossreact with both self- and foreign- major histocompatibility complex (MHC) proteins in an enigmatic phenomenon termed alloreactivity. Here we present the 2.35 angstrom structure of the 2C TCR complexed with its foreign ligand H-2L(d)-QL9. Surprisingly, we find that this TCR utilizes a different strategy to engage the foreign pMHC in comparison to the manner in which it recognizes a self ligand H-2K(b)-dEV8. 2C engages both shared and polymorphic residues on L-d and K-b, as well as the unrelated QL9 and dEV8 peptide antigens, in unique pair-wise contacts, resulting in greater structural complementarity with the L-d-QL9 complex. In the structure of an engineered, high-affinity 2C TCR variant bound to H-2L(d)- QL9, the "wild-type" TCR-MHC binding orientation persists despite modified TCR-CDR3 alpha interactions with peptide. Thus, a single TCR recognizes two globally similar, but distinct ligands by divergent mechanisms, indicating that receptor-ligand crossreactivity can occur in the absence of molecular mimicry.