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

PJ Brennan, RVV Tatituri, M Brigl, EY Kim, A Tuli… - Nature …, 2011 - nature.com
PJ Brennan, RVV Tatituri, M Brigl, EY Kim, A Tuli, JP Sanderson, SD Gadola, FF Hsu
Nature immunology, 2011nature.com
Invariant natural killer T cells (i NKT 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 i NKT cell self antigen in mouse and …
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.
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