Structural basis of plasticity in T cell receptor recognition of a self peptide MHC antigen
Structural basis of plasticity in T cell receptor recognition of a self peptide MHC antigen
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DOI：
10.1126/science.279.5354.1166
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发表时间：
1998-02-20
期刊：
影响因子：
56.9
通讯作者：
Wilson, IA
中科院分区：
文献类型：
--
作者：
Garcia, KC;Degano, M;Wilson, IA
T细胞受体(TCR)具有双重特异性，T细胞在成熟过程中必须识别胸腺中的自身抗原，然后区分周围的外来病原体。这种交叉反应的分子基础是通过与自体主要组织相容性复合体(PMHC)抗原H-2K(B)-dEV8结合的同种异体反应2C TCR的晶体结构来阐明的，根据各向异性3.0 Angstrom分辨率X射线数据进行精炼，肽和TCR之间的界面表现出极差的形状互补性，而TCRβ链互补决定区3(CDR3)与dEV8的相互作用最小。TCR CDR环中的三个在结合时被诱导出较大的构象变化，提供了一种结构可塑性的机制来适应各种不同的多肽抗原，广泛的TCR与pMHCα螺旋的相互作用表明了一种由TCR的V-α结构域介导的普遍取向，并使TCR如何有效地“扫描”结合在一个大的、低亲和力的MHC结构框架内的不同多肽，以寻找那些提供信号所需的轻微额外的动力学稳定的多肽。
The T cell receptor (TCR) inherently has dual specificity, T cells must recognize self-antigens in the thymus during maturation and then discriminate between foreign pathogens in the periphery, A molecular basis for this cross-reactivity is elucidated by the crystal structure of the alloreactive 2C TCR bound to self peptide-major histocompatibility complex (pMHC) antigen H-2K(b)-dEV8 refined against anisotropic 3.0 angstrom resolution x-ray data, The interface between peptide and TCR exhibits extremely poor shape complementarity, and the TCR beta chain complementarity-determining region 3 (CDR3) has minimal interaction with the dEV8 peptide, Large conformational changes in three of the TCR CDR loops are induced upon binding, providing a mechanism of structural plasticity to accommodate a variety of different peptide antigens, Extensive TCR interaction with the pMHC alpha helices suggests a generalized orientation that is mediated by the V-alpha domain of the TCR and rationalizes how TCRs can effectively "scan" different peptides bound within a large, low-affinity MHC structural framework for those that provide the slight additional kinetic stabilization required for signaling.