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

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, Gurdyal Besra, Amy R Howell, Lorenzo Moretta, James McCluskey, Mirjam H M Heemskerk, Stephanie Gras, Jamie Rossjohn, Dale I Godfrey

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

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.

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

Fingerprint

Dive into the research topics of 'The molecular bases of δ/αβ T cell-mediated antigen recognition'. Together they form a unique fingerprint.

Cite this