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

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

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21 Citations (Scopus)


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


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