The T-cell receptor is not hardwired to engage MHC ligands

被引：24

作者：

Holland, Stephen J. ^{[1
,2
]}

Bartok, Istvan ^{[1
]}

Attaf, Meriem ^{[1
]}

Genolet, Raphael ^{[3
]}

Luescher, Immanuel F. ^{[3
]}

Kotsiou, Eleni ^{[1
,4
]}

Richard, Ashkenaz ^{[1
]}

Wang, Edward ^{[1
]}

White, Matthew ^{[1
]}

Coe, David J. ^{[1
]}

Chai, Jian-Guo ^{[1
]}

Ferreira, Cristina ^{[1
]}

Dyson, Julian ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Div Immunol & Inflammat, Mol Immunol Sect, London W12 0NN, England

[2] Max Planck Inst Immunol & Epigenet, Dept Dev Immunol, D-79108 Freiburg, Germany

[3] Ludwig Inst Canc Res, Mol Immunol Grp, Lausanne Branch, CH-1066 Epalinges, Switzerland

[4] Queen Mary Univ London, Barts Canc Inst, Ctr Haematooncol, London EC1M 6BQ, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 45期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金; 英国医学研究理事会;

关键词：

MHC restriction; TCR; MAJOR HISTOCOMPATIBILITY COMPLEX; PEPTIDE-MHC; NEGATIVE SELECTION; POSITIVE SELECTION; THYMIC SELECTION; AMINO-ACIDS; CLASS-I; ANTIGEN; SPECIFICITY; MOUSE;

D O I：

10.1073/pnas.1210882109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The bias of alpha beta T cells for MHC ligands has been proposed to be intrinsic to the T-cell receptor (TCR). Equally, the CD4 and CD8 coreceptors contribute to ligand restriction by colocalizing Lck with the TCR when MHC ligands are engaged. To determine the importance of intrinsic ligand bias, the germ-line TCR complementarity determining regions were extensively diversified in vivo. We show that engagement with MHC ligands during thymocyte selection and peripheral T-cell activation imposes remarkably little constraint over TCR structure. Such versatility is more consistent with an opportunist, rather than a predetermined, mode of interface formation. This hypothesis was experimentally confirmed by expressing a hybrid TCR containing TCR-gamma chain germ-line complementarity determining regions, which engaged efficiently with MHC ligands.

引用

页码：E3111 / E3118

页数：8

共 42 条

[1] T Cell Receptor Signaling Is Limited by Docking Geometry to Peptide-Major Histocompatibility Complex [J].