CD1d-lipid antigen recognition by the γδ TCR

Adam P Uldrich, Jerome Le Nours, Daniel G Pellicci, Nicholas A Gherardin, Kristy G McPherson, Ricky T Lim, Onisha Patel, Travis Clarke Beddoe, Stephanie Gras, Jamie Rossjohn, Dale I Godfrey

Research output: Contribution to journalArticleResearchpeer-review

136 Citations (Scopus)

Abstract

The T cell repertoire comprises alphabeta and gammadelta T cell lineages. Although it is established how alphabeta T cell antigen receptors (TCRs) interact with antigen presented by antigen-presenting molecules, this is unknown for gammadelta TCRs. We describe a population of human Vdelta1(+) gammadelta T cells that exhibit autoreactivity to CD1d and provide a molecular basis for how a gammadelta TCR binds CD1d-alpha-galactosylceramide (alpha-GalCer). The gammadelta TCR docked orthogonally, over the A pocket of CD1d, in which the Vdelta1-chain, and in particular the germ line-encoded CDR1delta loop, dominated interactions with CD1d. The TCR gamma-chain sat peripherally to the interface, with the CDR3gamma loop representing the principal determinant for alpha-GalCer specificity. Accordingly, we provide insight into how a gammadelta TCR binds specifically to a lipid-loaded antigen-presenting molecule.
Original languageEnglish
Pages (from-to)1137-1145
Number of pages9
JournalNature Immunology
Volume14
Issue number11
DOIs
Publication statusPublished - 2013

Cite this

Uldrich, A. P., Le Nours, J., Pellicci, D. G., Gherardin, N. A., McPherson, K. G., Lim, R. T., ... Godfrey, D. I. (2013). CD1d-lipid antigen recognition by the γδ TCR. Nature Immunology, 14(11), 1137-1145. https://doi.org/10.1038/ni.2713
Uldrich, Adam P ; Le Nours, Jerome ; Pellicci, Daniel G ; Gherardin, Nicholas A ; McPherson, Kristy G ; Lim, Ricky T ; Patel, Onisha ; Beddoe, Travis Clarke ; Gras, Stephanie ; Rossjohn, Jamie ; Godfrey, Dale I. / CD1d-lipid antigen recognition by the γδ TCR. In: Nature Immunology. 2013 ; Vol. 14, No. 11. pp. 1137-1145.
@article{fe9b0accfc154f4bbe221edf7a8e01a9,
title = "CD1d-lipid antigen recognition by the γδ TCR",
abstract = "The T cell repertoire comprises alphabeta and gammadelta T cell lineages. Although it is established how alphabeta T cell antigen receptors (TCRs) interact with antigen presented by antigen-presenting molecules, this is unknown for gammadelta TCRs. We describe a population of human Vdelta1(+) gammadelta T cells that exhibit autoreactivity to CD1d and provide a molecular basis for how a gammadelta TCR binds CD1d-alpha-galactosylceramide (alpha-GalCer). The gammadelta TCR docked orthogonally, over the A pocket of CD1d, in which the Vdelta1-chain, and in particular the germ line-encoded CDR1delta loop, dominated interactions with CD1d. The TCR gamma-chain sat peripherally to the interface, with the CDR3gamma loop representing the principal determinant for alpha-GalCer specificity. Accordingly, we provide insight into how a gammadelta TCR binds specifically to a lipid-loaded antigen-presenting molecule.",
author = "Uldrich, {Adam P} and {Le Nours}, Jerome and Pellicci, {Daniel G} and Gherardin, {Nicholas A} and McPherson, {Kristy G} and Lim, {Ricky T} and Onisha Patel and Beddoe, {Travis Clarke} and Stephanie Gras and Jamie Rossjohn and Godfrey, {Dale I}",
year = "2013",
doi = "10.1038/ni.2713",
language = "English",
volume = "14",
pages = "1137--1145",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "11",

}

Uldrich, AP, Le Nours, J, Pellicci, DG, Gherardin, NA, McPherson, KG, Lim, RT, Patel, O, Beddoe, TC, Gras, S, Rossjohn, J & Godfrey, DI 2013, 'CD1d-lipid antigen recognition by the γδ TCR', Nature Immunology, vol. 14, no. 11, pp. 1137-1145. https://doi.org/10.1038/ni.2713

CD1d-lipid antigen recognition by the γδ TCR. / Uldrich, Adam P; Le Nours, Jerome; Pellicci, Daniel G; Gherardin, Nicholas A; McPherson, Kristy G; Lim, Ricky T; Patel, Onisha; Beddoe, Travis Clarke; Gras, Stephanie; Rossjohn, Jamie; Godfrey, Dale I.

In: Nature Immunology, Vol. 14, No. 11, 2013, p. 1137-1145.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - CD1d-lipid antigen recognition by the γδ TCR

AU - Uldrich, Adam P

AU - Le Nours, Jerome

AU - Pellicci, Daniel G

AU - Gherardin, Nicholas A

AU - McPherson, Kristy G

AU - Lim, Ricky T

AU - Patel, Onisha

AU - Beddoe, Travis Clarke

AU - Gras, Stephanie

AU - Rossjohn, Jamie

AU - Godfrey, Dale I

PY - 2013

Y1 - 2013

N2 - The T cell repertoire comprises alphabeta and gammadelta T cell lineages. Although it is established how alphabeta T cell antigen receptors (TCRs) interact with antigen presented by antigen-presenting molecules, this is unknown for gammadelta TCRs. We describe a population of human Vdelta1(+) gammadelta T cells that exhibit autoreactivity to CD1d and provide a molecular basis for how a gammadelta TCR binds CD1d-alpha-galactosylceramide (alpha-GalCer). The gammadelta TCR docked orthogonally, over the A pocket of CD1d, in which the Vdelta1-chain, and in particular the germ line-encoded CDR1delta loop, dominated interactions with CD1d. The TCR gamma-chain sat peripherally to the interface, with the CDR3gamma loop representing the principal determinant for alpha-GalCer specificity. Accordingly, we provide insight into how a gammadelta TCR binds specifically to a lipid-loaded antigen-presenting molecule.

AB - The T cell repertoire comprises alphabeta and gammadelta T cell lineages. Although it is established how alphabeta T cell antigen receptors (TCRs) interact with antigen presented by antigen-presenting molecules, this is unknown for gammadelta TCRs. We describe a population of human Vdelta1(+) gammadelta T cells that exhibit autoreactivity to CD1d and provide a molecular basis for how a gammadelta TCR binds CD1d-alpha-galactosylceramide (alpha-GalCer). The gammadelta TCR docked orthogonally, over the A pocket of CD1d, in which the Vdelta1-chain, and in particular the germ line-encoded CDR1delta loop, dominated interactions with CD1d. The TCR gamma-chain sat peripherally to the interface, with the CDR3gamma loop representing the principal determinant for alpha-GalCer specificity. Accordingly, we provide insight into how a gammadelta TCR binds specifically to a lipid-loaded antigen-presenting molecule.

UR - http://www.nature.com/ni/journal/v14/n11/pdf/ni.2713.pdf

U2 - 10.1038/ni.2713

DO - 10.1038/ni.2713

M3 - Article

VL - 14

SP - 1137

EP - 1145

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 11

ER -

Uldrich AP, Le Nours J, Pellicci DG, Gherardin NA, McPherson KG, Lim RT et al. CD1d-lipid antigen recognition by the γδ TCR. Nature Immunology. 2013;14(11):1137-1145. https://doi.org/10.1038/ni.2713