Germline-encoded recognition of diverse glycolipids by natural killer T cells

James P Scott-Browne, Jennifer L Matsuda, Thierry Mallevaey, Janice White, Natalie Borg, James McCluskey, Jamie Rossjohn, John Kappler, Philippa Marrack, Laurent Gapin

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134 Citations (Scopus)


Natural killer T cells expressing invariant T cell receptor alpha-chains (TCRalpha chains) containing variable (V) and joining (J) region V(alpha)14-J(alpha)18 (V(alpha)14i) rearrangements recognize both endogenous and microbial glycolipids in the context of CD1d. How cells expressing an invariant TCRalpha chain and a restricted set of TCRbeta chains recognize structurally diverse antigens is not clear. Here we show that a V(alpha)14i TCR recognized many alpha-linked glycolipids by means of a hot-spot of germline-encoded amino acids in complementarity-determining regions 3alpha, 1alpha and 2beta. This hot-spot did not shift during the recognition of structurally distinct antigens, suggesting that the V(alpha)14i TCR functions as a pattern-recognition receptor, conferring on natural killer T cells the ability to sense and respond in an innate way to pathogens displaying antigenic alpha-linked glycolipids.
Original languageEnglish
Pages (from-to)1105 - 1113
Number of pages9
JournalNature Immunology
Issue number10
Publication statusPublished - 2007

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