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

281 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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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",

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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

UR - https://www.scopus.com/pages/publications/84886726570

U2 - 10.1038/ni.2713

DO - 10.1038/ni.2713

M3 - Article

SN - 1529-2908

VL - 14

SP - 1137

EP - 1145

JO - Nature Immunology

JF - Nature Immunology

IS - 11

ER -

CD1d-lipid antigen recognition by the γδ TCR

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