title: Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens.
abstract: Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex. However, the diversity of the NKT cell repertoire and the ensuing interactions with CD1d-antigen remain unclear. We describe an atypical population of CD1d-α-galactosylceramide (α-GalCer)-reactive human NKT cells that differ markedly from the prototypical TRAV10-TRAJ18-TRBV25-1(+) type I NKT cell repertoire. These cells express a range of TCR α- and β-chains that show differential recognition of glycolipid antigens. Two atypical NKT TCRs (TRAV21-TRAJ8-TRBV7-8 and TRAV12-3-TRAJ27-TRBV6-5) bind orthogonally over the A'-pocket of CD1d, adopting distinct docking modes that contrast with the docking mode of all type I NKT TCR-CD1d-antigen complexes. Moreover, the interactions with α-GalCer differ between the type I and these atypical NKT TCRs. Accordingly, diverse NKT TCR repertoire usage manifests in varied docking strategies and specificities towards CD1d-α-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition.
authors.affiliation: Infection and Immunity Program &Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.|Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Le Nours
authors.affiliation: Infection and Immunity Program &Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Praveena
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia.|Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, Victoria 3000, 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, Melbourne, Victoria 3000, Australia.|Cancer Immunology Research Program, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Gherardin
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia.|Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Ross
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Ricky T
authors.initials: RT
authors.lastname: Lim
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Gurdyal S
authors.identifier: http://orcid.org/0000-0002-5605-0395
authors.initials: GS
authors.lastname: Besra
authors.affiliation: Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060, USA.
authors.forename: Santosh
authors.identifier: http://orcid.org/0000-0002-9375-2230
authors.initials: S
authors.lastname: Keshipeddy
authors.affiliation: Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060, USA.
authors.forename: Stewart K
authors.initials: SK
authors.lastname: Richardson
authors.affiliation: Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060, USA.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Howell
authors.affiliation: Infection and Immunity Program &Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.|Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia.|Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.affiliation: Infection and Immunity Program &Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.|Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.|Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
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, Melbourne, Victoria 3000, Australia.|Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Uldrich
mesh_terms: D055610:Antigens, CD1d / Q000276:immunology*; D018360:Crystallography, X-Ray; D005699:Galactosylceramides / Q000276:immunology*; D005732:Gangliosides / Q000276:immunology; D005963:Glucosylceramides / Q000276:immunology; D006801:Humans; D008055:Lipids / Q000276:immunology; D062105:Molecular Docking Simulation; D055611:Natural Killer T-Cells / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human; D005699:Galactosylceramides; D005732:Gangliosides; D005963:Glucosylceramides; D008055:Lipids; D016693:Receptors, Antigen, T-Cell, alpha-beta; C493154:alpha-galactosylceramide