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


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, ?-D-glucopyranosylceramide (?-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, ?-GlcCer accumulated during infection and in response to Toll-like receptor agonists, contributing to iNKT cell activation. Thus, we propose that recognition of ?-GlcCer by the invariant T cell antigen receptor translates innate danger signals into iNKT cell activation.

SUBMITTER: Brennan PJ 

PROVIDER: S-EPMC3242449 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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

Brennan Patrick J PJ   Tatituri Raju V V RV   Brigl Manfred M   Kim Edy Y EY   Tuli Amit A   Sanderson Joseph P JP   Gadola Stephan D SD   Hsu Fong-Fu FF   Besra Gurdyal S GS   Brenner Michael B MB  

Nature immunology 20111030 12


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 c  ...[more]

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