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 journalArticle

24 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, CD1dlipid 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
Pages (from-to)2599-2615
Number of pages17
JournalJournal of Experimental Medicine
Volume211
Issue number13
DOIs
Publication statusPublished - 2014

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T-Cell Antigen Receptor
T-Lymphocytes
Antigens
Natural Killer T-Cells
CD1d Antigen
Galactosylceramides
Glucosylceramides
Lipids
T-Cell Receptor Genes
Cell Lineage
HLA Antigens
Cell Biology
Immune System
Peptides
Population
Genes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Pellicci, D. G., Uldrich, A. P., Le Nours, J., Ross, F., Chabrol, E., Eckle, S. B. G., ... Godfrey, D. I. (2014). The molecular bases of δ/αβ T cell-mediated antigen recognition. Journal of Experimental Medicine, 211(13), 2599-2615. https://doi.org/10.1084/jem.20141764

The molecular bases of δ/αβ T cell-mediated antigen recognition. / Pellicci, Daniel G.; Uldrich, Adam P.; Le Nours, Jérôme; Ross, Fiona; Chabrol, Eric; Eckle, Sidonia B G; de Boer, Renate; Lim, Ricky T.; McPherson, Kirsty; Besra, Gurdyal; Howell, Amy R.; Moretta, Lorenzo; McCluskey, James; Heemskerk, Mirjam H M; Gras, Stephanie; Rossjohn, Jamie; Godfrey, Dale I.

In: Journal of Experimental Medicine, Vol. 211, No. 13, 2014, p. 2599-2615.

Research output: Contribution to journalArticle

Pellicci, DG, Uldrich, AP, Le Nours, J, Ross, F, Chabrol, E, Eckle, SBG, de Boer, R, Lim, RT, McPherson, K, Besra, G, Howell, AR, Moretta, L, McCluskey, J, Heemskerk, MHM, Gras, S, Rossjohn, J & Godfrey, DI 2014, 'The molecular bases of δ/αβ T cell-mediated antigen recognition', Journal of Experimental Medicine, vol. 211, no. 13, pp. 2599-2615. https://doi.org/10.1084/jem.20141764
Pellicci DG, Uldrich AP, Le Nours J, Ross F, Chabrol E, Eckle SBG et al. The molecular bases of δ/αβ T cell-mediated antigen recognition. Journal of Experimental Medicine. 2014;211(13):2599-2615. https://doi.org/10.1084/jem.20141764
Pellicci, Daniel G. ; Uldrich, Adam P. ; Le Nours, Jérôme ; Ross, Fiona ; Chabrol, Eric ; Eckle, Sidonia B G ; de Boer, Renate ; Lim, Ricky T. ; McPherson, Kirsty ; Besra, Gurdyal ; Howell, Amy R. ; Moretta, Lorenzo ; McCluskey, James ; Heemskerk, Mirjam H M ; Gras, Stephanie ; Rossjohn, Jamie ; Godfrey, Dale I. / The molecular bases of δ/αβ T cell-mediated antigen recognition. In: Journal of Experimental Medicine. 2014 ; Vol. 211, No. 13. pp. 2599-2615.
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AU - Chabrol, Eric

AU - Eckle, Sidonia B G

AU - de Boer, Renate

AU - Lim, Ricky T.

AU - McPherson, Kirsty

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AU - Howell, Amy R.

AU - Moretta, Lorenzo

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AU - Heemskerk, Mirjam H M

AU - Gras, Stephanie

AU - Rossjohn, Jamie

AU - Godfrey, Dale I.

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