细胞色素 c-I-E(k)特异性 T 细胞受体特异性和交叉反应性的结构基础
Structural basis of specificity and cross-reactivity in T cell receptors specific for cytochrome c-I-E(k).
机构信息
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
出版信息
J Immunol. 2011 May 15;186(10):5823-32. doi: 10.4049/jimmunol.1100197. Epub 2011 Apr 13.
Abstract
T cells specific for the cytochrome c Ag are widely used to investigate many aspects of TCR specificity and interactions with peptide-MHC, but structural information has long been elusive. In this study, we present structures for the well-studied 2B4 TCR, as well as a naturally occurring variant of the 5c.c7 TCR, 226, which is cross-reactive with more than half of possible substitutions at all three TCR-sensitive residues on the peptide Ag. These structures alone and in complex with peptide-MHC ligands allow us to reassess many prior mutagenesis results. In addition, the structure of 226 bound to one peptide variant, p5E, shows major changes in the CDR3 contacts compared with wild-type, yet the TCR V-region contacts with MHC are conserved. These and other data illustrate the ability of TCRs to accommodate large variations in CDR3 structure and peptide contacts within the constraints of highly conserved TCR-MHC interactions.
摘要
T 细胞特异性细胞色素 c Ag 被广泛用于研究 TCR 特异性和与肽-MHC 相互作用的多个方面，但结构信息一直难以捉摸。在这项研究中，我们呈现了经过充分研究的 2B4 TCR 的结构，以及 5c.c7 TCR 的一种自然发生的变体 226 的结构，该变体与肽 Ag 上所有三个 TCR 敏感残基的一半以上的可能取代物交叉反应。这些结构本身以及与肽-MHC 配体的复合物使我们能够重新评估许多先前的诱变结果。此外，与一种肽变体 p5E 结合的 226 的结构与野生型相比，CDR3 接触发生了重大变化，但 TCR V 区与 MHC 的接触保持不变。这些和其他数据说明了 TCR 能够在高度保守的 TCR-MHC 相互作用的限制内，适应 CDR3 结构和肽接触的较大变化。
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