A Molecular Basis for NKT Cell Recognition of CD1d-Self-Antigen

被引：114

作者：

Mallevaey, Thierry ^{[2
]}

Clarke, Andrew J. ^{[1
]}

Scott-Browne, James P. ^{[2
]}

Young, Mary H. ^{[2
]}

Roisman, Laila C. ^{[1
]}

Pellicci, Daniel G. ^{[3
]}

Patel, Onisha ^{[1
]}

Vivian, Julian P. ^{[1
]}

Matsuda, Jennifer L. ^{[2
]}

McCluskey, James ^{[3
]}

Godfrey, Dale I. ^{[3
]}

Marrack, Philippa ^{[2
,4
,5
,6
]}

Rossjohn, Jamie ^{[1
]}

Gapin, Laurent ^{[2
]}

机构：

[1] Monash Univ, ARC Ctr Excellence Struct & Funct Microbial Genom, Prot Crystallog Unit, Dept Biochem & Mol Biol,Sch Biomed Sci, Clayton, Vic 3800, Australia

[2] Univ Colorado, Sch Med & Natl Jewish Hlth, Dept Immunol, Denver, CO 80206 USA

[3] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia

[4] Univ Colorado Denver, Howard Hughes Med Inst, Denver, CO 80220 USA

[5] Univ Colorado Denver, Dept Med, Denver, CO 80220 USA

[6] Univ Colorado Denver, Dept Biochem & Mol Genet, Denver, CO 80220 USA

来源：

IMMUNITY | 2011年 / 34卷 / 03期

基金：

美国国家卫生研究院; 澳大利亚国家健康与医学研究理事会; 英国医学研究理事会; 澳大利亚研究理事会;

关键词：

KILLER T-CELLS; STRUCTURAL BASIS; CUTTING EDGE; RECEPTOR; CD1D; ACTIVATION; GLYCOLIPIDS; REPERTOIRE; COMPLEX; SELF;

D O I：

10.1016/j.immuni.2011.01.013

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The antigen receptor for natural killer T cells (NKT TCR) binds CD1d-restricted microbial and self-lipid antigens, although the molecular basis of self-CD1d recognition is unclear. Here, we have characterized NKT TCR recognition of CD1d molecules loaded with 0 natural self-antigens (Ags) and report the 2.3 angstrom resolution structure of an autoreactive NKT TCR-phosphatidylinositol-CD1d complex. NKT TCR recognition of self- and foreign antigens was underpinned by a similar mode of germline-encoded recognition of CD1d. However, NKT TCR autoreactivity is mediated by unique sequences within the non-germline-encoded CDR3 beta loop encoding for a hydrophobic motif that promotes self-association with CD1d. Accordingly, NKT cell autoreactivity may arise from the inherent affinity of the interaction between CD1d and the NKT TCR, resulting in the recognition of a broad range of CD1d-restricted self-antigens. This demonstrates that multiple self-antigens can be recognized in a similar manner by autoreactive NKT TCRs.

引用

页码：315 / 326

页数：12

共 49 条

[31] Activation of invariant NKT cells by toll-like receptor 9-stimulated dendritic cells requires type I interferon and charged Glycosphingolipids [J].