超激动剂TCR/MHC复合物中抗原识别的功能性热点。

A functional hot spot for antigen recognition in a superagonist TCR/MHC complex.

作者信息

Degano M, Garcia K C, Apostolopoulos V, Rudolph M G, Teyton L, Wilson I A

机构信息

Department of Molecular Biology and Skaggs Institute for Chemical Biology, La Jolla, California 92037, USA.

出版信息

Immunity. 2000 Mar;12(3):251-61. doi: 10.1016/s1074-7613(00)80178-8.

DOI:10.1016/s1074-7613(00)80178-8

PMID:10755612

Abstract

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-2Kb with superagonist peptide SIYR at 2.8 A 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 3alpha, 3beta, and 1beta, 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.

摘要

T细胞受体信号传导中一个长期存在的问题是，结构相似、亲和力相近的配体如何能具有截然不同的生物学活性。H-2Kb与超激动剂肽SIYR形成的2C TCR复合物在2.8埃分辨率下的晶体结构阐明了TCR区分改变的肽配体的结构基础。抗原效力的差异由TCR结合位点的两个腔室调节，这两个腔室主要由互补决定区（CDR）3α、3β和1β形成，与位于中央的肽残基互补。这个“功能热点”使TCR能够在不同配体间能量相似的相互作用中，精准区分出那些肽能适当稳定TCR/pMHC复合物的相互作用，为理解T细胞交叉反应性产生的差异信号传导提供了新的结构视角。