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

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

Research output: Contribution to journalArticleResearchpeer-review

24 Citations (Scopus)

Abstract

alphabeta and gammadelta T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the alphabeta and gammadelta T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term delta/alphabeta T cells, expressing TCRs comprised of a TCR-delta variable gene (Vdelta1) fused to joining alpha and constant alpha domains, paired with an array of TCR-beta chains. We demonstrate that these cells, which represent approximately 50 of all Vdelta1+ 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 delta/alphabeta T cells recognized alpha-galactosylceramide (alpha-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as alpha-glucosylceramide, was distinct from type I NKT cells. Thus, delta/alphabetaTCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how delta/alphabetaTCRs bind to their targets, with the Vdelta1-encoded region providing a major contribution to delta/alphabetaTCR binding. Our findings highlight how components from alphabeta and gammadeltaTCR 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

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
Pellicci, Daniel G ; Uldrich, Adam P ; Le Nours, Jerome ; Ross, Fiona ; Chabrol, Eric ; Eckle, Sidonia B G ; de Boer, Renate ; Lim, Ricky T ; McPherson, Kristy G ; Besra, Gurdyal S ; 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.
@article{ac48cb5cd41a4725816c999295cb6d9b,
title = "The molecular bases of δ/αβ T cell-mediated antigen recognition",
abstract = "alphabeta and gammadelta T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the alphabeta and gammadelta T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term delta/alphabeta T cells, expressing TCRs comprised of a TCR-delta variable gene (Vdelta1) fused to joining alpha and constant alpha domains, paired with an array of TCR-beta chains. We demonstrate that these cells, which represent approximately 50 of all Vdelta1+ 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 delta/alphabeta T cells recognized alpha-galactosylceramide (alpha-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as alpha-glucosylceramide, was distinct from type I NKT cells. Thus, delta/alphabetaTCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how delta/alphabetaTCRs bind to their targets, with the Vdelta1-encoded region providing a major contribution to delta/alphabetaTCR binding. Our findings highlight how components from alphabeta and gammadeltaTCR gene loci can recombine to confer Ag specificity, thus expanding our understanding of T cell biology and TCR diversity.",
author = "Pellicci, {Daniel G} and Uldrich, {Adam P} and {Le Nours}, Jerome and Fiona Ross and Eric Chabrol and Eckle, {Sidonia B G} and {de Boer}, Renate and Lim, {Ricky T} and McPherson, {Kristy G} and Besra, {Gurdyal S} and Howell, {Amy R} and Lorenzo Moretta and James McCluskey and Heemskerk, {Mirjam H M} and Stephanie Gras and Jamie Rossjohn and Godfrey, {Dale I}",
year = "2014",
doi = "10.1084/jem.20141764",
language = "English",
volume = "211",
pages = "2599--2615",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "13",

}

Pellicci, DG, Uldrich, AP, Le Nours, J, Ross, F, Chabrol, E, Eckle, SBG, de Boer, R, Lim, RT, McPherson, KG, Besra, GS, 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

The molecular bases of δ/αβ T cell-mediated antigen recognition. / Pellicci, Daniel G; Uldrich, Adam P; Le Nours, Jerome; Ross, Fiona; Chabrol, Eric; Eckle, Sidonia B G; de Boer, Renate; Lim, Ricky T; McPherson, Kristy G; Besra, Gurdyal S; 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 journalArticleResearchpeer-review

TY - JOUR

T1 - The molecular bases of δ/αβ T cell-mediated antigen recognition

AU - Pellicci, Daniel G

AU - Uldrich, Adam P

AU - Le Nours, Jerome

AU - Ross, Fiona

AU - Chabrol, Eric

AU - Eckle, Sidonia B G

AU - de Boer, Renate

AU - Lim, Ricky T

AU - McPherson, Kristy G

AU - Besra, Gurdyal S

AU - Howell, Amy R

AU - Moretta, Lorenzo

AU - McCluskey, James

AU - Heemskerk, Mirjam H M

AU - Gras, Stephanie

AU - Rossjohn, Jamie

AU - Godfrey, Dale I

PY - 2014

Y1 - 2014

N2 - alphabeta and gammadelta T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the alphabeta and gammadelta T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term delta/alphabeta T cells, expressing TCRs comprised of a TCR-delta variable gene (Vdelta1) fused to joining alpha and constant alpha domains, paired with an array of TCR-beta chains. We demonstrate that these cells, which represent approximately 50 of all Vdelta1+ 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 delta/alphabeta T cells recognized alpha-galactosylceramide (alpha-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as alpha-glucosylceramide, was distinct from type I NKT cells. Thus, delta/alphabetaTCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how delta/alphabetaTCRs bind to their targets, with the Vdelta1-encoded region providing a major contribution to delta/alphabetaTCR binding. Our findings highlight how components from alphabeta and gammadeltaTCR gene loci can recombine to confer Ag specificity, thus expanding our understanding of T cell biology and TCR diversity.

AB - alphabeta and gammadelta T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the alphabeta and gammadelta T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term delta/alphabeta T cells, expressing TCRs comprised of a TCR-delta variable gene (Vdelta1) fused to joining alpha and constant alpha domains, paired with an array of TCR-beta chains. We demonstrate that these cells, which represent approximately 50 of all Vdelta1+ 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 delta/alphabeta T cells recognized alpha-galactosylceramide (alpha-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as alpha-glucosylceramide, was distinct from type I NKT cells. Thus, delta/alphabetaTCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how delta/alphabetaTCRs bind to their targets, with the Vdelta1-encoded region providing a major contribution to delta/alphabetaTCR binding. Our findings highlight how components from alphabeta and gammadeltaTCR gene loci can recombine to confer Ag specificity, thus expanding our understanding of T cell biology and TCR diversity.

UR - http://jem.rupress.org/content/211/13/2599.full.pdf+html

U2 - 10.1084/jem.20141764

DO - 10.1084/jem.20141764

M3 - Article

VL - 211

SP - 2599

EP - 2615

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 13

ER -