Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs

Raju V.V. Tatituri, Gerald F.M. Watts, Veemal Bhowruth, Nathaniel Barton, Alissa Rothchild, Fong Fu Hsu, Catarina F. Almeida, Liam R. Cox, Lothar Eggeling, Susanna Cardell, Jamie Rossjohn, Dale I. Godfrey, Samuel M. Behar, Gurdyal S. Besra, Michael B. Brenner, Manfred Brigl

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

CD1d-restricted natural killer T (NKT) cells include two major subgroups. The most widely studied are Vα14Jα18+ invariant NKT (iNKT) cells that recognize the prototypical α-galactosylceramide antigen, whereas the other major group uses diverse T-cell receptor (TCR) α-and β-chains, does not recognize α-galactosylceramide, and is referred to as diverse NKT (dNKT) cells. dNKT cells play important roles during infection and autoimmunity, but the antigens they recognize remain poorly understood. Here, we identified phosphatidylglycerol (PG), diphosphatidylglycerol (DPG, or cardiolipin), and phosphatidylinositol from Mycobacterium tuberculosis or Corynebacterium glutamicum as microbial antigens that stimulated various dNKT, but not iNKT, hybridomas. dNKT hybridomas showed distinct reactivities for diverse antigens. Stimulation ofdNKT hybridomas by microbial PG was independent of Toll-like receptormediated signaling by antigen-presenting cells and required lipid uptake and/or processing. Furthermore, microbial PG bound to CD1d molecules and plate-bound PG/CD1d complexes stimulated dNKT hybridomas, indicating direct recognition by the dNKT cell TCR. Interestingly, despite structural differences in acyl chain composition between microbial and mammalian PG and DPG, lipids from both sources stimulated dNKT hybridomas, suggesting that presentation of microbial lipids and enhanced availability of stimulatory self-lipids may both contribute to dNKT cell activation during infection.

Original languageEnglish
Pages (from-to)1827-1832
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number5
DOIs
StatePublished - Jan 29 2013

Keywords

  • Adaptive immunity
  • CD1 antigen presentation
  • Innate immunity
  • Type II natural killer T cell

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