A semi-invariant V{alpha}10{+} T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen-recognition properties

Adam Uldrich, Onisha Patel, Garth Cameron, Daniel Pellicci, E Bridie Day, Lucy Sullivan, Konstantinos Kyparissoudis, Lars Kjer-Nielsen, Julian Vivian, Benjamin Cao, Andrew Brooks, Spencer Williams, Petr Illarionov, Gurdyal Besra, Stephen Turner, Steven Porcelli, James McCluskey, Mark Smyth, Jamie Rossjohn, Dale Godfrey

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83 Citations (Scopus)

Abstract

Type I natural killer T cells (NKT cells) are characterized by an invariant variable region 14-joining region 18 (V(alpha)14-J(alpha)18) T cell antigen receptor (TCR) alpha-chain and recognition of the glycolipid alpha-galactosylceramide (alpha-GalCer) restricted to the antigen-presenting molecule CD1d. Here we describe a population of alpha-GalCer-reactive NKT cells that expressed a canonical V(alpha)10-J(alpha)50 TCR alpha-chain, which showed a preference for alpha-glucosylceramide (alpha-GlcCer) and bacterial alpha-glucuronic acid-containing glycolipid antigens. Structurally, despite very limited TCRalpha sequence identity, the V(alpha)10 TCR-CD1d-alpha-GlcCer complex had a docking mode similar to that of type I TCR-CD1d-alpha-GalCer complexes, although differences at the antigen-binding interface accounted for the altered antigen specificity. Our findings provide new insight into the structural basis and evolution of glycolipid antigen recognition and have notable implications for the scope and immunological role of glycolipid-specific T cell responses.
Original languageEnglish
Pages (from-to)616 - 623
Number of pages8
JournalNature Immunology
Volume12
Issue number7
DOIs
Publication statusPublished - 2011

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