title: Identification of a Potent Microbial Lipid Antigen for Diverse NKT Cells.
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.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Wolf
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Raju V V
authors.initials: RV
authors.lastname: Tatituri
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging at University of Melbourne, Parkville, Victoria 3010, Australia;
authors.forename: Catarina F
authors.initials: CF
authors.lastname: Almeida
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia;
authors.forename: Jérôme
authors.initials: J
authors.lastname: Le Nours
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom;
authors.forename: Veemal
authors.initials: V
authors.lastname: Bhowruth
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging at University of Melbourne, Parkville, Victoria 3010, Australia;
authors.forename: Darryl
authors.initials: D
authors.lastname: Johnson
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging at University of Melbourne, Parkville, Victoria 3010, Australia;
authors.forename: Adam P
authors.initials: AP
authors.lastname: Uldrich
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research, Washington University, St. Louis, MO 63110;
authors.forename: Fong-Fu
authors.initials: FF
authors.lastname: Hsu
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; and.
authors.forename: Manfred
authors.initials: M
authors.lastname: Brigl
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom;
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia; Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging at University of Melbourne, Parkville, Victoria 3010, Australia;
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; mbrenner@research.bwh.harvard.edu.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D055610:Antigens, CD1d / Q000276:immunology; D002460:Cell Line; D006825:Hybridomas / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology*; D008563:Membrane Lipids / Q000276:immunology*; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology*; D010715:Phosphatidylglycerols / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D000941:Antigens; D055610:Antigens, CD1d; C584692:CD1d antigen, mouse; D008563:Membrane Lipids; D010715:Phosphatidylglycerols