A conserved human T cell population targets mycobacterial antigens presented by CD1b

被引：163

作者：

Van Rhijn, Ildiko ^{[1
,2
]}

Kasmar, Anne ^{[1
]}

de Jong, Annemieke ^{[1
]}

Gras, Stephanie ^{[3
]}

Bhati, Mugdha ^{[3
]}

Doorenspleet, Marieke E. ^{[4
]}

de Vries, Niek ^{[4
]}

Godfrey, Dale I. ^{[5
]}

Altman, John D. ^{[6
]}

de Jager, Wilco ^{[7
]}

Rossjohn, Jamie ^{[3
,8
]}

Moody, D. Branch ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Rheumatol & Immunol, Brigham & Womens Hosp, Boston, MA 02115 USA

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

[3] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic, Australia

[4] Univ Amsterdam, Acad Med Ctr, Dept Clin Immunol & Rheumatol, NL-1012 WX Amsterdam, Netherlands

[5] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia

[6] NIH Tetramer Core Facil, Emory Vaccine Ctr, Atlanta, GA USA

[7] Univ Utrecht, Med Ctr, Dept Pediat Immunol, Utrecht, Netherlands

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

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 07期

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

LIPID ANTIGENS; RECOGNITION; EXPRESSION; RESPONSES; MEMORY; LYMPHOCYTES;

D O I：

10.1038/ni.2630

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：

Human T cell antigen receptors (TCRs) pair in millions of combinations to create complex and unique T cell repertoires for each person. Through the use of tetramers to analyze TCRs reactive to the antigen-presenting molecule CD1b, we detected T cells with highly stereotyped TCR alpha-chains present among genetically unrelated patients with tuberculosis. The germline-encoded, mycolyl lipid-reactive (GEM) TCRs had an alpha-chain bearing the variable (V) region TRAV1-2 rearranged to the joining (J) region TRAJ9 with few nontemplated (N)-region additions. Analysis of TCRs by high-throughput sequencing, binding and crystallography showed linkage of TCR alpha sequence motifs to high-affinity recognition of antigen. Thus, the CD1-reactive TCR repertoire is composed of at least two compartments: high-affinity GEM TCRs, and more-diverse TCRs with low affinity for CD1b-lipid complexes. We found high interdonor conservation of TCRs that probably resulted from selection by a nonpolymorphic antigen-presenting molecule and an immunodominant antigen.

引用

页码：706 / +

页数：10

共 48 条

[1]

RECOGNITION OF A LIPID ANTIGEN BY CD1-RESTRICTED ALPHA-BETA(+) T-CELLS [J].