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

doi:10.1038/ni.2713

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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › Research › peer-review

172 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 language	English
Pages (from-to)	1137-1145
Number of pages	9
Journal	Nature Immunology
Volume	14
Issue number	11
DOIs	https://doi.org/10.1038/ni.2713
Publication status	Published - 2013

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@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",

}

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 journal › Article › Research › peer-review

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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

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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.

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