Butyrophilin 3A1 binds phosphorylated antigens and stimulates human γδ T cells

被引：332

作者：

Vavassori, Stefano ^{[1
]}

Kumar, Anil ^{[2
]}

Wan, Gan Siok ^{[2
]}

Ramanjaneyulu, Gundimeda S. ^{[1
]}

Cavallari, Marco ^{[1
]}

El Daker, Sary ^{[2
]}

Beddoe, Travis ^{[3
]}

Theodossis, Alex ^{[3
]}

Williams, Neal K. ^{[3
]}

Gostick, Emma ^{[4
]}

Price, David A. ^{[4
]}

Soudamini, Dinish U. ^{[5
]}

Voon, Kong Kien ^{[5
]}

Olivo, Malini ^{[5
]}

Rossjohn, Jamie ^{[3
,4
]}

Mori, Lucia ^{[1
,2
]}

De Libero, Gennaro ^{[1
,2
]}

机构：

[1] Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland

[2] Agcy Sci Technol & Res, Singapore Immunol Network, Singapore, Singapore

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

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

[5] Agcy Sci Technol & Res, Singapore Bioimaging Consortium, Singapore, Singapore

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 09期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

PRENYL PYROPHOSPHATE ANTIGENS; NONPEPTIDE ANTIGENS; MULTIPLE-SCLEROSIS; CRYSTAL-STRUCTURE; MOLECULES; RECOGNITION; ACTIVATION; RECEPTOR; COMPLEX; METABOLITES;

D O I：

10.1038/ni.2665

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Human T cells that express a T cell antigen receptor (TCR) containing g-chain variable region 9 and gamma-chain variable region 2 (V(gamma)9V(delta)2) recognize phosphorylated prenyl metabolites as antigens in the presence of antigen-presenting cells but independently of major histocompatibility complex (MHC), the MHC class I-related molecule MR1 and antigen-presenting CD1 molecules. Here we used genetic approaches to identify the molecule that binds and presents phosphorylated antigens. We found that the butyrophilin BTN3A1 bound phosphorylated antigens with low affinity, at a stoichiometry of 1:1, and stimulated mouse T cells with transgenic expression of a human V(gamma)9V(delta)2 TCR. The structures of the BTN3A1 distal domain in complex with host-or microbe-derived phosphorylated antigens had an immunoglobulin-like fold in which the antigens bound in a shallow pocket. Soluble V(gamma)9V(delta)2 TCR interacted specifically with BTN3A1-antigen complexes. Accordingly, BTN3A1 represents an antigen-presenting molecule required for the activation of V(gamma)9V(delta)2 T cells.

引用

页码：908 / +

页数：11

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[1] The Adaptable Major Histocompatibility Complex (MHC) Fold: Structure and Function of Nonclassical and MHC Class I-Like Molecules [J].