A Molecular Basis for the Exquisite CD1d-Restricted Antigen Specificity and Functional Responses of Natural Killer T Cells

被引：105

作者：

Wun, Kwok S. ^{[2
]}

Cameron, Garth ^{[1
]}

Patel, Onisha ^{[2
]}

Pang, Siew Siew ^{[2
]}

Pellicci, Daniel G. ^{[1
]}

Sullivan, Lucy C. ^{[1
]}

Keshipeddy, Santosh ^{[3
]}

Young, Mary H. ^{[4
,5
]}

Uldrich, Adam P. ^{[1
]}

Thakur, Meena S. ^{[3
]}

Richardson, Stewart K. ^{[3
]}

Howell, Amy R. ^{[3
]}

Illarionov, Petr A. ^{[6
]}

Brooks, Andrew G. ^{[1
]}

Besra, Gurdyal S. ^{[6
]}

McCluskey, James ^{[1
]}

Gapin, Laurent ^{[4
,5
]}

Porcelli, Steven A. ^{[7
]}

Godfrey, Dale I. ^{[1
]}

Rossjohn, Jamie ^{[2
]}

机构：

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

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

[3] Univ Connecticut, Dept Chem, Storrs, CT 06269 USA

[4] Univ Colorado Denver, Dept Immunol, Denver, CO 80206 USA

[5] Natl Jewish Hlth, Denver, CO 80206 USA

[6] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England

[7] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA

来源：

IMMUNITY | 2011年 / 34卷 / 03期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

NKT CELLS; RECOGNITION; RECEPTOR; TCR; ACTIVATION; KINETICS; LIGANDS; SELECTION; VARIANTS; AFFINITY;

D O I：

10.1016/j.immuni.2011.02.001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Natural killer T (NKT) cells respond to a variety of CD1d-restricted antigens (Ags), although the basis for Ag discrimination by the NKT cell receptor (TCR) is unclear. Here we have described NKT TCR fine specificity against several closely related Ags, termed altered glycolipid ligands (AGLs), which differentially stimulate NKT cells. The structures of five ternary complexes all revealed similar docking. Acyl chain modifications did not affect the interaction, but reduced NKT cell proliferation, indicating an affect on Ag processing or presentation. Conversely, truncation of the phytosphingosine chain caused an induced fit mode of TCR binding that affected TCR affinity. Modifications in the glycosyl head group had a direct impact on the TCR interaction and associated cellular response, with ligand potency reflecting the t(1/2) life of the interaction. Accordingly, we have provided a molecular basis for understanding how modifications in AGLs can result in striking alterations in the cellular response of NKT cells.

引用

页码：327 / 339

页数：13

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