Journal article

Structural determination of lipid antigens captured at the CD1d-T-cell receptor interface

Patrick J Brennan, Tan-Yun Cheng, Daniel G Pellicci, Gerald FM Watts, Natacha Veerapen, David C Young, Jamie Rossjohn, Gurdyal S Besra, Dale I Godfrey, Michael B Brenner, D Branch Moody

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2017

Abstract

Glycolipid antigens recognized by αβ T-cell receptors (TCRs) drive the activation of invariant natural killer T (iNKT) cells, a specialized subset of innate T lymphocytes. Glycolipids with α-linked anomeric carbohydrates have been identified as potent microbial lipid antigens for iNKT cells, and their unusual α-anomeric linkage has been thought to define a "foreign" lipid antigen motif. However, mammals use endogenous lipids to select iNKT cells, and there is compelling evidence for iNKT cell responses in various types of sterile inflammation. The nature of endogenous or environmental lipid antigens encountered by iNKT cells is not well defined. Here, we sought to identify lipid antigens in ..

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Grants

Awarded by NIH


Awarded by National Health and Medical Research Council of Australia


Awarded by Australian Research Council


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Funding Acknowledgements

We thank C. Costello, C. Heiss, and P. Azadi for helpful discussions and J. Buter for assistance with figure production. This study was supported in part by NIH Grant AI102945 (to P.J.B.); the Violin and Karol families (P.J.B.); NIH Grants AR048632 and AI111224 (to D.B.M.); the Bill and Melinda Gates Foundation (D.B.M.); NIH Grants AI113046 and AI063428 (to M.B.B.); J. Badrick, the Royal Society, and the Medical Research Council (G.S.B.); National Health and Medical Research Council of Australia Grants 1013667, 1113293, 1020770, 1117766, and 1054431 (to D.I.G. and D.G.P.); Australian Research Council Grant CE140100011 (to D.I.G. and D.G.P.); and Australian Research Council Grants FL160100049 and CE140100011 (to J.R.).