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

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 languageEnglish
Pages (from-to)1137-1145
Number of pages9
JournalNature Immunology
Volume14
Issue number11
DOIs
Publication statusPublished - 2013

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