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 journalArticlepeer-review

239 Citations (Scopus)


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)1202-11
Number of pages10
JournalNature Immunology
Issue number12
Publication statusPublished - Dec 2011


  • Animals
  • Autoantigens
  • Autoimmunity
  • Bacterial Infections
  • Cell Line
  • Glycosphingolipids
  • Humans
  • Lymphocyte Activation
  • Lymphoid Tissue
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Killer T-Cells
  • Receptors, Antigen, T-Cell


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