A functional hot spot for antigen recognition in a superagonist TCR/MHC complex
A functional hot spot for antigen recognition in a superagonist TCR/MHC complex
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DOI：
10.1016/s1074-7613(00)80178-8
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发表时间：
2000-03-01
期刊：
影响因子：
32.4
通讯作者：
Wilson, IA
中科院分区：
文献类型：
--
作者：
Degano, M;Garcia, KC;Wilson, IA
在T细胞受体信号传导中，一个长期存在的问题是，具有相似亲和力的结构相似的配体如何具有本质上不同的生物活性。H-2K(b)与超激动剂肽SIYR的2C TCR复合物在2.8埃下的晶体结构阐明了TCR识别改变的肽配体的结构基础。抗原效价的差异是由TCR结合位点的两个空腔调节的，主要由cdr 3 α、3 β和1 β组成，它们补充了位于中心的肽残基。这个“功能热点”允许TCR精细区分不同配体内能量相似的相互作用，其中肽适当地稳定了TCR/pMHC复合物，并为理解T细胞交叉反应性引起的差异信号传导提供了新的结构视角。
A longstanding question in T cell receptor signaling is how structurally similar ligands, with similar affinities, can have substantially different biological activity. The crystal structure of the 2C TCR complex of H-2K(b) with superagonist peptide SIYR at 2.8 Angstrom elucidates a structural basis for TCR discrimination of altered peptide ligands. The difference in antigen potency is modulated by two cavities in the TCR combining site, formed mainly by CDRs 3 alpha, 3 beta, and 1 beta, that complement centrally located peptide residues. This "functional hot spot" allows the TCR to finely discriminate amongst energetically similar interactions within different ligands for those in which the peptide appropriately stabilizes the TCR/pMHC complex and provides a new structural perspective for understanding differential signaling resulting from T cell cross-reactivity.