The CDR3 regions of an immunodominant T cell receptor dictate the 'energetic landscape' of peptide-MHC recognition

被引：154

作者：

Borg, NA

Ely, LK

Beddoe, T

Macdonald, WA

Reid, HH

Clements, CS

Purcell, AW

Kjer-Nielsen, L

Miles, JJ

Burrows, SR

McCluskey, J

Rossjohn, J ^{[1
]}

机构：

[1] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia

[2] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Monash Ctr Synchrotron Sci,Prot Crystallog Unit, Clayton, Vic 3800, Australia

[3] Queensland Inst Med Res, Cellular Immunol Lab, Brisbane, Qld 4029, Australia

来源：

NATURE IMMUNOLOGY | 2005年 / 6卷 / 02期

基金：

澳大利亚研究理事会; 英国惠康基金; 英国医学研究理事会;

关键词：

D O I：

10.1038/ni1155

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The energetic bases of T cell recognition are unclear. Here, we studied the 'energetic landscape' of peptide-major histocompatibility complex (pMHC) recognition by an immunodominant alphabeta T cell receptor (TCR). We quantified and evaluated the effect of natural and systematic substitutions in the complementarity-determining region (CDR) loops on ligand binding in the context of the structural detail of each component of the immunodominant TCR-pMHC complex. The CDR1 and CDR2 loops contributed minimal energy through direct recognition of the antigen and instead had a chief function in stabilizing the ligated CDR3 loops. The underlying energetic basis for recognition lay in the CDR3 loops. Therefore the energetic burden of the CDR loops in the TCR-pMHC interaction is variable among TCRs, reflecting the inherent adaptability of the TCR in ligating different ligands.

引用

收藏

页码：171 / 180

页数：10

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