T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex

被引：113

作者：

Beringer, Dennis X. ^{[1
,2
]}

Kleijwegt, Fleur S. ^{[3
]}

Wiede, Florian ^{[1
,2
]}

van der Slik, Arno R. ^{[3
]}

Loh, Khai Lee ^{[1
,2
]}

Petersen, Jan ^{[1
,2
,4
]}

Dudek, Nadine L. ^{[1
,2
]}

Duinkerken, Gaby ^{[3
]}

Laban, Sandra ^{[3
]}

Joosten, Antoinette ^{[3
]}

Vivian, Julian P. ^{[1
,2
,4
]}

Chen, Zhenjun ^{[5
]}

Uldrich, Adam P. ^{[5
,6
]}

Godfrey, Dale I. ^{[5
,6
]}

McCluskey, James ^{[5
]}

Price, David A. ^{[7
,8
]}

Radford, Kristen J. ^{[9
,10
]}

Purcell, Anthony W. ^{[1
,2
]}

Nikolic, Tatjana ^{[3
]}

Reid, Hugh H. ^{[1
,2
,4
]}

Tiganis, Tony ^{[1
,2
]}

Roep, Bart O. ^{[3
]}

Rossjohn, Jamie ^{[1
,2
,4
,7
]}

机构：

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

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

[3] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands

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

[5] Univ Melbourne, Australian Res Council Ctr Excellence Adv Mol Ima, Parkville, Vic 3052, Australia

[6] Univ Melbourne, Dept Microbiol & Immunol, Peter Doherty Inst Infect & Immun, Parkville, Vic 3052, Australia

[7] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales

[8] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[9] Univ Queensland, Mater Res Inst, Brisbane, Qld, Australia

[10] Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia

来源：

NATURE IMMUNOLOGY | 2015年 / 16卷 / 11期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

STRUCTURAL BASIS; DENDRITIC CELLS; GERMLINE BIAS; CLASS-I; MHC; TCR; TOLERANCE; RESPONSES; USAGE; CD4;

D O I：

10.1038/ni.3271

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Central to adaptive immunity is the interaction between the alpha beta T cell receptor (TCR) and peptide presented by the major histocompatibility complex (MHC) molecule. Presumably reflecting TCR-MHC bias and T cell signaling constraints, the TCR universally adopts a canonical polarity atop the MHC. We report the structures of two TCRs, derived from human induced T regulatory (iT(reg)) cells, complexed to an MHC class II molecule presenting a proinsulin-derived peptide. The ternary complexes revealed a 1800 polarity reversal compared to all other TCR-peptide-MHC complex structures. Namely, the iT(reg) TCR alpha-chain and beta-chain are overlaid with the alpha-chain and beta-chain of MHC class II, respectively. Nevertheless, this TCR interaction elicited a peptide-reactive, MHC-restricted T cell signal. Thus TCRs are not 'hardwired' to interact with MHC molecules in a stereotypic manner to elicit a T cell signal, a finding that fundamentally challenges our understanding of TCR recognition.

引用

页码：1153 / 1161

页数：9

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