Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens

Research output: Contribution to journalArticlepeer-review


  • Jérôme Le Nours
  • T Praveena
  • Daniel G Pellicci
  • Nicholas A Gherardin
  • Fiona J Ross
  • Ricky T Lim
  • Santosh Keshipeddy
  • Stewart K Richardson
  • Amy R Howell
  • Stephanie Gras
  • Dale I Godfrey
  • Jamie Rossjohn
  • Adam P Uldrich

Colleges, School and Institutes


Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex. However, the diversity of the NKT cell repertoire and the ensuing interactions with CD1d-antigen remain unclear. We describe an atypical population of CD1d-α-galactosylceramide (α-GalCer)-reactive human NKT cells that differ markedly from the prototypical TRAV10-TRAJ18-TRBV25-1(+) type I NKT cell repertoire. These cells express a range of TCR α- and β-chains that show differential recognition of glycolipid antigens. Two atypical NKT TCRs (TRAV21-TRAJ8-TRBV7-8 and TRAV12-3-TRAJ27-TRBV6-5) bind orthogonally over the A'-pocket of CD1d, adopting distinct docking modes that contrast with the docking mode of all type I NKT TCR-CD1d-antigen complexes. Moreover, the interactions with α-GalCer differ between the type I and these atypical NKT TCRs. Accordingly, diverse NKT TCR repertoire usage manifests in varied docking strategies and specificities towards CD1d-α-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition.


Original languageEnglish
Article number10570
JournalNature Communications
Publication statusPublished - 15 Feb 2016


  • Biological sciences, Immunology, Molecular biology