Identification of a potent microbial lipid antigen for diverse NKT cells

Benjamin J. Wolf, Raju V.V. Tatituri, Catarina F. Almeida, Jérôme Le Nours, Veemal Bhowruth, Darryl Johnson, Adam P. Uldrich, Fong Fu Hsu, Manfred Brigl, Gurdyal S. Besra, Jamie Rossjohn, Dale I. Godfrey, Michael B. Brenner

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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 Listeriaderived 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.

Original languageEnglish
Pages (from-to)2540-2551
Number of pages12
JournalJournal of Immunology
Volume195
Issue number6
DOIs
StatePublished - Sep 15 2015

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