T cell receptor recognition of CD1b presenting a mycobacterial glycolipid

被引：54

作者：

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

Van Rhijn, Ildiko ^{[4
,5
]}

Shahine, Adam ^{[1
,2
,3
]}

Cheng, Tan-Yun ^{[4
]}

Bhati, Mugdha ^{[1
,2
]}

Tan, Li Lynn ^{[1
,2
]}

Halim, Hanim ^{[1
,2
]}

Tuttle, Kathryn D. ^{[6
,7
]}

Gapin, Laurent ^{[6
,7
]}

Le Nours, Jerome ^{[1
,2
,3
]}

Moody, D. Branch ^{[4
]}

Rossjohn, Jamie ^{[1
,2
,3
,8
]}

机构：

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

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

[3] Monash Univ, Ctr Excellence Adv Mol Imaging, Australian Res Council, Clayton, Vic, Australia

[4] Harvard Med Sch, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA

[5] Univ Utrecht, Fac Vet Med, Dept Infect Dis & Immunol, Utrecht, Netherlands

[6] Univ Colorado, Dept Immunol & Microbiol, Anschutz Med Campus, Aurora, CO USA

[7] Natl Jewish Hlth, Aurora, CO USA

[8] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff, S Glam, Wales

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

CRYSTAL-STRUCTURE; ANTIGEN; COMPLEX; TETRAMERS; ANGSTROM; FEATURES; BIOLOGY; BIAS;

D O I：

10.1038/ncomms13257

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：

CD1 proteins present microbial lipids to T cells. Germline-encoded mycolyl lipid-reactive (GEM) T cells with conserved ab T cell receptors (TCRs) recognize CD1b presenting mycobacterial mycolates. As the molecular basis underpinning TCR recognition of CD1b remains unknown, here we determine the structure of a GEM TCR bound to CD1b presenting glucose-6-O-monomycolate (GMM). The GEM TCR docks centrally above CD1b, whereby the conserved TCR alpha-chain extensively contacts CD1b and GMM. Through mutagenesis and study of T cells from tuberculosis patients, we identify a consensus CD1b footprint of TCRs present among GEM Tcells. Using both the TCR alpha-and beta-chains as tweezers to surround and grip the glucose moiety of GMM, GEM TCRs create a highly specific mechanism for recognizing this mycobacterial glycolipid.

引用

页数：12

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