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

Research output: Contribution to journalArticlepeer-review

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

  • Monash University
  • 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.
  • University of Melbourne
  • Cardiff University

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