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

  • Nat Commun. 2016 Feb 15;7:10570. doi: 10.1038/ncomms10570.
Jérôme Le Nours  1  2 ,  T Praveena  1 ,  Daniel G Pellicci  3  4 ,  Nicholas A Gherardin  3  5 ,  Fiona J Ross  3  4 ,  Ricky T Lim  3 ,  Gurdyal S Besra  6 ,  Santosh Keshipeddy  7 ,  Stewart K Richardson  7 ,  Amy R Howell  7 ,  Stephanie Gras  1  2 ,  Dale I Godfrey  3  4 ,  Jamie Rossjohn  1  2  8 ,  Adam P Uldrich  3  4
Affiliations
  • 1. Infection and Immunity Program &Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
  • 2. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
  • 3. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia.
  • 4. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, Victoria 3000, Australia.
  • 5. Cancer Immunology Research Program, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.
  • 6. School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
  • 7. Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060, USA.
  • 8. Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
PMID: 26875526 DOI: 10.1038/ncomms10570
Abstract

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.