Ligand-engaged TCR is triggered by Lck not associated with CD8 coreceptor

被引：62

作者：

Casas, Javier ^{[1
,2
]}

Brzostek, Joanna ^{[1
,2
]}

Zarnitsyna, Veronika I. ^{[3
,4
]}

Hong, Jin-sung ^{[4
,5
]}

Wei, Qianru ^{[1
]}

Hoerter, John A. H. ^{[2
]}

Fu, Guo ^{[2
]}

Ampudia, Jeanette ^{[2
]}

Zamoyska, Rose ^{[6
]}

Zhu, Cheng ^{[3
,4
,5
]}

Gascoigne, Nicholas R. J. ^{[1
,2
]}

机构：

[1] Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Microbiol, Singapore 117545, Singapore

[2] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[3] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA

[4] Emory Univ, Atlanta, GA 30332 USA

[5] Georgia Inst Technol, George W Woodruff Sch Mech Engn, Atlanta, GA 30332 USA

[6] Univ Edinburgh, Inst Immunol & Infect Res, Edinburgh EH9 3FL, Midlothian, Scotland

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

英国惠康基金;

关键词：

SRC-FAMILY KINASES; CELL-RECEPTOR INTERACTION; IMMUNOLOGICAL SYNAPSE; ACTIVATION; FRET; DIFFERENTIATION; REVEALS; BINDING; SIGNAL; FYN;

D O I：

10.1038/ncomms6624

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 earliest molecular events in T-cell recognition have not yet been fully described, and the initial T-cell receptor (TCR)-triggering mechanism remains a subject of controversy. Here, using total internal reflection/Forster resonance energy transfer microscopy, we observe a two-stage interaction between TCR, CD8 and major histocompatibility complex (MHC)peptide. There is an early (within seconds) interaction between CD3 zeta and the coreceptor CD8 that is independent of the binding of CD8 to MHC, but that requires CD8 association with Lck. Later (several minutes) CD3 zeta-CD8 interactions require CD8-MHC binding. Lck can be found free or bound to the coreceptor. This work indicates that the initial TCR-triggering event is induced by free Lck.

引用

页数：11

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