The molecular bases of δ/αβ T cell-mediated antigen recognition

Research output: Contribution to journalArticle

Authors

  • Daniel G Pellicci
  • Adam P Uldrich
  • Jérôme Le Nours
  • Fiona Ross
  • Eric Chabrol
  • Sidonia B G Eckle
  • Renate de Boer
  • Ricky T Lim
  • Kirsty McPherson
  • Amy R Howell
  • Lorenzo Moretta
  • James McCluskey
  • Mirjam H M Heemskerk
  • Stephanie Gras
  • Jamie Rossjohn
  • Dale I Godfrey

Colleges, School and Institutes

External organisations

  • 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.
  • 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.
  • 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 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 Hematology, Leiden University Medical Center, 2300 RC Leiden, Netherlands.
  • Department of Chemistry, University of Connecticut, Storrs, CT 06269.
  • Istituto Giannina Gaslini, 16147 Genova, Italy.
  • 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.
  • 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.

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.

Bibliographic note

© 2014 Pellicci et al.

Details

Original languageEnglish
JournalThe Journal of Experimental Medicine
Publication statusPublished - 1 Dec 2014