CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor

Natalie Borg, Kwok Soon Wun, Lars Kjer-Nielsen, Matthew Charles James Wilce, Daniel G Pellicci, Ruide Koh, Gurdyal S Besra, Mandvi Bharadwaj, Dale I Godfrey, James McCluskey, Jamie Rossjohn

Research output: Contribution to journalArticleResearchpeer-review

442 Citations (Scopus)

Abstract

The CD1 family is a large cluster of non-polymorphic, major histocompatibility complex (MHC) class-I-like molecules that bind distinct lipid-based antigens that are recognized by T cells. The most studied group of T cells that interact with lipid antigens are natural killer T (NKT) cells, which characteristically express a semi-invariant T-cell receptor (NKT TCR) that specifically recognizes the CD1 family member, CD1d. NKT-cell-mediated recognition of the CD1d?antigen complex has been implicated in microbial immunity, tumour immunity, autoimmunity and allergy. Here we describe the structure of a human NKT TCR in complex with CD1d bound to the potent NKT-cell agonist -galactosylceramide, the archetypal CD1d-restricted glycolipid. In contrast to T-cell receptor?peptide-antigen?MHC complexes, the NKT TCR docked parallel to, and at the extreme end of the CD1d-binding cleft, which enables a lock-and-key type interaction with the lipid antigen. The structure provides a basis for the interaction between the highly conserved NKT TCR -chain and the CD1d?antigen complex that is typified in innate immunity, and also indicates how variability of the NKT TCR -chain can impact on recognition of other CD1d?antigen complexes. These findings provide direct insight into how a T-cell receptor recognizes a lipid-antigen-presenting molecule of the immune system.
Original languageEnglish
Pages (from-to)44 - 49
Number of pages6
JournalNature
Volume448
Issue number7149
Publication statusPublished - 2007

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