title: Antigen Specificity of Type I NKT Cells Is Governed by TCR β-Chain Diversity.
abstract: NKT cells recognize lipid-based Ags presented by CD1d. Type I NKT cells are often referred to as invariant owing to their mostly invariant TCR α-chain usage (Vα14-Jα18 in mice, Vα24-Jα18 in humans). However, these cells have diverse TCR β-chains, including Vβ8, Vβ7, and Vβ2 in mice and Vβ11 in humans, joined to a range of TCR Dβ and Jβ genes. In this study, we demonstrate that TCR β-chain composition can dramatically influence lipid Ag recognition in an Ag-dependent manner. Namely, the glycolipids α-glucosylceramide and isoglobotrihexosylceramide were preferentially recognized by Vβ7(+) NKT cells from mice, whereas the α-galactosylceramide analog OCH, with a truncated sphingosine chain, was preferentially recognized by Vβ8(+) NKT cells from mice. We show that the influence of the TCR β-chain is due to a combination of Vβ-, Jβ-, and CDR3β-encoded residues and that these TCRs can recapitulate the selective Ag reactivity in TCR-transduced cell lines. Similar observations were made with human NKT cells where different CDR3β-encoded residues determined Ag preference. These findings indicate that NKT TCR β-chain diversity results in differential and nonhierarchical Ag recognition by these cells, which implies that some Ags can preferentially activate type I NKT cell subsets.
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, University of Melbourne, Parkville, Victoria 3010, Australia;
authors.forename: Garth
authors.initials: G
authors.lastname: Cameron
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, University of Melbourne, Parkville, Victoria 3010, Australia;
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pellicci
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, University of Melbourne, Parkville, Victoria 3010, Australia;
authors.forename: Adam P
authors.initials: AP
authors.lastname: Uldrich
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: School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom;
authors.forename: Petr
authors.initials: P
authors.lastname: Illarionov
authors.affiliation: School of Chemistry, University of Melbourne, Parkville, Victoria 3010, Australia; Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia;
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Williams
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia;
authors.forename: Nicole L
authors.initials: NL
authors.lastname: La Gruta
authors.affiliation: Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia; and Institute of Infection and Immunity, Cardiff University School of Medicine, 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, University of Melbourne, Parkville, Victoria 3010, Australia; godfrey@unimelb.edu.au.
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000276:immunology*; D019674:Genes, T-Cell Receptor beta / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005915:Globosides / Q000276:immunology; D005963:Glucosylceramides / Q000276:immunology*; D006801:Humans; D008055:Lipids / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D014281:Trihexosylceramides / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; C584692:CD1d antigen, mouse; D005915:Globosides; D005963:Glucosylceramides; D008055:Lipids; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014281:Trihexosylceramides; C514781:isoglobotrihexosylceramide