Dependence of T Cell Antigen Recognition on T Cell Receptor-Peptide MHC Confinement Time

被引：178

作者：

Aleksic, Milos ^{[1
]}

Dushek, Omer ^{[1
,2
]}

Zhang, Hao ^{[1
]}

Shenderov, Eugene ^{[3
,4
]}

Chen, Ji-Li ^{[3
]}

Cerundolo, Vincenzo ^{[3
]}

Coombs, Daniel ^{[5
,6
]}

van der Merwe, P. Anton ^{[1
]}

机构：

[1] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

[2] Univ Oxford, Ctr Math Biol, Oxford OX1 3LB, England

[3] Univ Oxford, Weatherall Inst Mol Med, Oxford OX3 9DS, England

[4] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA

[5] Univ British Columbia, Dept Math, Vancouver, BC V6T 1Z2, Canada

[6] Univ British Columbia, Inst Appl Math, Vancouver, BC V6T 1Z2, Canada

来源：

IMMUNITY | 2010年 / 32卷 / 02期

基金：

英国医学研究理事会;

关键词：

MAJOR HISTOCOMPATIBILITY COMPLEX; LIGAND INTERACTIONS; BINDING-KINETICS; TCR-BINDING; ACTIVATION; AFFINITY; FLEXIBILITY; VACCINES; DESIGN; IMMUNOGENICITY;

D O I：

10.1016/j.immuni.2009.11.013

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

T cell receptor (TCR) binding to diverse peptide-major histocompatibility complex (pMHC) ligands results in various degrees of T cell activation. Here we analyze which binding properties of the TCR-pMHC interaction are responsible for this variation in pMHC activation potency. We have analyzed activation of the 1G4 cytotoxic T lymphocyte clone by cognate pMHC variants and performed thorough correlation analysis of T cell activation with 1134 TCR-pMHC binding properties measured in solution. We found that both the on rate (k(on)) and off rate (k(off)) contribute to activation potency. Based on our results, we propose a model in which rapid TCR rebinding to the same pMHC after chemical dissociation increases the effective half-life or "confinement time" of a TCR-pMHC interaction. This confinement time model clarifies the role of k(on) in T cell activation and reconciles apparently contradictory repo on the role of TCR-pMHC binding kinetics and affinity in T cell activation.

引用

页码：163 / 174

页数：12

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