Identification of a potent microbial lipid antigen for diverse NKT cells

Research output: Contribution to journalArticlepeer-review

Authors

  • Benjamin J Wolf
  • Raju V V Tatituri
  • Catarina F Almeida
  • Jérôme Le Nours
  • Darryl Johnson
  • Adam P Uldrich
  • Fong-Fu Hsu
  • Manfred Brigl
  • Jamie Rossjohn
  • Dale I Godfrey
  • Michael B Brenner

Colleges, School and Institutes

Abstract

Semi-invariant/type I NKT cells are a well-characterized CD1d-restricted T cell subset. The availability of potent Ags and tetramers for semi-invariant/type I NKT cells allowed this population to be extensively studied and revealed their central roles in infection, autoimmunity, and tumor immunity. In contrast, diverse/type II NKT (dNKT) cells are poorly understood because the lipid Ags that they recognize are largely unknown. We sought to identify dNKT cell lipid Ag(s) by interrogating a panel of dNKT mouse cell hybridomas with lipid extracts from the pathogen Listeria monocytogenes. We identified Listeria phosphatidylglycerol as a microbial Ag that was significantly more potent than a previously characterized dNKT cell Ag, mammalian phosphatidylglycerol. Further, although mammalian phosphatidylglycerol-loaded CD1d tetramers did not stain dNKT cells, the Listeria-derived phosphatidylglycerol-loaded tetramers did. The structure of Listeria phosphatidylglycerol was distinct from mammalian phosphatidylglycerol because it contained shorter, fully-saturated anteiso fatty acid lipid tails. CD1d-binding lipid-displacement studies revealed that the microbial phosphatidylglycerol Ag binds significantly better to CD1d than do counterparts with the same headgroup. These data reveal a highly potent microbial lipid Ag for a subset of dNKT cells and provide an explanation for its increased Ag potency compared with the mammalian counterpart.

Bibliographic note

Copyright © 2015 by The American Association of Immunologists, Inc.

Details

Original languageEnglish
Pages (from-to)2540-2551
Number of pages12
JournalJournal of Immunology
Volume195
Issue number6
Early online date4 Sep 2015
Publication statusPublished - 15 Sep 2015