Canonical T cell receptor docking on peptide-MHC is essential for T cell signaling

被引：58

作者：

Zareie, Pirooz ^{[1
,2
]}

Szeto, Christopher ^{[1
,2
,3
]}

Farenc, Carine ^{[1
,2
]}

Gunasinghe, Sachith D. ^{[4
,5
]}

Kolawole, Elizabeth M. ^{[6
]}

Nguyen, Angela ^{[1
,2
]}

Blyth, Chantelle ^{[1
,2
]}

Sng, Xavier Y. X. ^{[1
,2
]}

Li, Jasmine ^{[1
,7
]}

Jones, Claerwen M. ^{[1
,2
]}

Fulcher, Alex J. ^{[8
]}

Jacobs, Jesica R. ^{[6
]}

Wei, Qianru ^{[10
]}

Wojciech, Lukasz ^{[9
,10
]}

Petersen, Jan ^{[1
,2
,11
]}

Gascoigne, Nicholas R. J. ^{[9
,10
]}

Evavold, Brian D. ^{[6
]}

Gaus, Katharina ^{[4
,5
]}

Gras, Stephanie ^{[1
,2
,3
,11
]}

Rossjohn, Jamie ^{[1
,2
,11
,12
]}

La Gruta, Nicole L. ^{[1
,2
]}

机构：

[1] Monash Univ, Biomed Discovery Inst, Infect & Immun Program, Clayton, Vic, Australia

[2] Monash Univ, Biomed Discovery Inst, Dept Biochem & Mol Biol, Clayton, Vic, Australia

[3] La Trobe Univ, La Trobe Inst Mol Sci, Dept Biochem & Genet, Melbourne, Vic, Australia

[4] Univ New South Wales, Sch Med Sci, Australia Node Single Mol Sci, EMBL, Sydney, NSW, Australia

[5] Univ New South Wales, Sch Med Sci, ARC Ctr Excellence Adv Mol Imaging, Sydney, NSW, Australia

[6] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA

[7] Monash Univ, Biomed Discovery Inst, Dept Microbiol, Clayton, Vic, Australia

[8] Monash Univ, Monash Micro Imaging, Clayton, Vic, Australia

[9] Natl Univ Singapore, Yong Loo Lin Sch Med, Immunol Translat Res Programme, Singapore 117545, Singapore

[10] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol & Immunol, Singapore 117545, Singapore

[11] Monash Univ, Australian Res Council Ctr Excellence Adv Mol Ima, Clayton, Vic, Australia

[12] Cardiff Univ, Sch Med, Inst Infect & Immun, Heath Pk, Cardiff, S Glam, Wales

来源：

SCIENCE | 2021年 / 372卷 / 6546期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会; 澳大利亚研究理事会;

关键词：

MACROMOLECULAR CRYSTALLOGRAPHY COMMUNITIES; THYMIC SELECTION; STRUCTURAL BASIS; TCR; RECOGNITION; COMPLEX; CD8; RESTRICTION; CORECEPTOR; LCK;

D O I：

10.1126/science.abe9124

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：

T cell receptor (TCR) recognition of peptide-major histocompatibility complexes (pMHCs) is characterized by a highly conserved docking polarity. Whether this polarity is driven by recognition or signaling constraints remains unclear. Using "reversed-docking" TCRb-variable (TRBV) 17(+) TCRs from the naive mouse CD8(+) T cell repertoire that recognizes the H-2D(b)-NP366 epitope, we demonstrate that their inability to support T cell activation and in vivo recruitment is a direct consequence of reversed docking polarity and not TCR-pMHCI binding or clustering characteristics. Canonical TCR-pMHCI docking optimally localizes CD8/Lck to the CD3 complex, which is prevented by reversed TCR-pMHCI polarity. The requirement for canonical docking was circumvented by dissociating Lck from CD8. Thus, the consensus TCR-pMHC docking topology is mandated by T cell signaling constraints.

引用

页码：1056 / +

页数：31

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