Identification of a potent microbial lipid antigen for diverse NKT cells

Benjamin J Wolf, Raju V V Tatituri, Catarina F Almeida, Jerome 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

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26 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)2540 - 2551
Number of pages12
JournalJournal of Immunology
Volume195
Issue number6
DOIs
Publication statusPublished - 2015

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