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

Research output: Contribution to journalArticle

Authors

  • NA Borg
  • KS Wun
  • L Kjer-Nielsen
  • MCJ Wilce
  • DG Pellicci
  • R Koh
  • M Bharadwaj
  • DI Godfrey
  • J McCluskey
  • J Rossjohn

Colleges, School and Institutes

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 alpha-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 alpha-chain and the CD1d - antigen complex that is typified in innate immunity, and also indicates how variability of the NKT TCR beta-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.

Details

Original languageEnglish
Pages (from-to)44-49
Number of pages6
JournalNature
Volume448
Issue number7149
Early online date20 Jun 2007
Publication statusPublished - 20 Jun 2007