Invariant natural killer T cells recognize lipid self antigen induced by microbial danger signals

Patrick J. Brennan, Raju V.V. Tatituri, Manfred Brigl, Edy Y. Kim, Amit Tuli, Joseph P. Sanderson, Stephan D. Gadola, Fong Fu Hsu, Gurdyal S. Besra, Michael B. Brenner

Research output: Contribution to journalArticle

229 Scopus citations

Abstract

Invariant natural killer T cells (iNKT cells) have a prominent role during infection and other inflammatory processes, and these cells can be activated through their T cell antigen receptors by microbial lipid antigens. However, increasing evidence shows that they are also activated in situations in which foreign lipid antigens would not be present, which suggests a role for lipid self antigen. We found that an abundant endogenous lipid, β-D- glucopyranosylceramide (β-GlcCer), was a potent iNKT cell self antigen in mouse and human and that its activity depended on the composition of the N-acyl chain. Furthermore, β-GlcCer accumulated during infection and in response to Toll-like receptor agonists, contributing to iNKT cell activation. Thus, we propose that recognition of β-GlcCer by the invariant T cell antigen receptor translates innate danger signals into iNKT cell activation.

Original languageEnglish
Pages (from-to)1202-1211
Number of pages10
JournalNature immunology
Volume12
Issue number12
DOIs
StatePublished - Dec 1 2011

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    Brennan, P. J., Tatituri, R. V. V., Brigl, M., Kim, E. Y., Tuli, A., Sanderson, J. P., Gadola, S. D., Hsu, F. F., Besra, G. S., & Brenner, M. B. (2011). Invariant natural killer T cells recognize lipid self antigen induced by microbial danger signals. Nature immunology, 12(12), 1202-1211. https://doi.org/10.1038/ni.2143