title: The molecular bases of δ/αβ T cell-mediated antigen recognition.
abstract: αβ and γδ T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the αβ and γδ T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term δ/αβ T cells, expressing TCRs comprised of a TCR-δ variable gene (Vδ1) fused to joining α and constant α domains, paired with an array of TCR-β chains. We demonstrate that these cells, which represent ∼50% of all Vδ1(+) human T cells, can recognize peptide- and lipid-based Ags presented by human leukocyte antigen (HLA) and CD1d, respectively. Similar to type I natural killer T (NKT) cells, CD1d-lipid Ag-reactive δ/αβ T cells recognized α-galactosylceramide (α-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as α-glucosylceramide, was distinct from type I NKT cells. Thus, δ/αβTCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how δ/αβTCRs bind to their targets, with the Vδ1-encoded region providing a major contribution to δ/αβTCR binding. Our findings highlight how components from αβ and γδTCR gene loci can recombine to confer Ag specificity, thus expanding our understanding of T cell biology and TCR diversity.
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and 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 and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and 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: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and 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: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: Ross
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Eric
authors.initials: E
authors.lastname: Chabrol
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Sidonia B G
authors.initials: SB
authors.lastname: Eckle
authors.affiliation: Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, Netherlands.
authors.forename: Renate
authors.initials: R
authors.lastname: de Boer
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Ricky T
authors.initials: RT
authors.lastname: Lim
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Kirsty
authors.initials: K
authors.lastname: McPherson
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, England, UK.
authors.forename: Gurdyal
authors.initials: G
authors.lastname: Besra
authors.affiliation: Department of Chemistry, University of Connecticut, Storrs, CT 06269.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Howell
authors.affiliation: Istituto Giannina Gaslini, 16147 Genova, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.affiliation: Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, Netherlands.
authors.forename: Mirjam H M
authors.initials: MH
authors.lastname: Heemskerk
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, Wales, UK jamie.rossjohn@monash.edu godfrey@unimelb.edu.au.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia jamie.rossjohn@monash.edu godfrey@unimelb.edu.au.
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
mesh_terms: D000595:Amino Acid Sequence; D055610:Antigens, CD1d / Q000276:immunology*; D002999:Clone Cells; D005699:Galactosylceramides / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D008055:Lipids / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D055610:Antigens, CD1d; D005699:Galactosylceramides; D008055:Lipids; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C493154:alpha-galactosylceramide