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

Author

Listed:
  • Jérôme Le Nours

    (Biomedicine Discovery Institute, Monash University
    Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University)

  • T. Praveena

    (Biomedicine Discovery Institute, Monash University)

  • Daniel G. Pellicci

    (Peter Doherty Institute for Infection and Immunity, University of Melbourne
    Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne)

  • Nicholas A. Gherardin

    (Peter Doherty Institute for Infection and Immunity, University of Melbourne
    Cancer Immunology Research Program, Peter MacCallum Cancer Centre)

  • Fiona J. Ross

    (Peter Doherty Institute for Infection and Immunity, University of Melbourne
    Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne)

  • Ricky T. Lim

    (Peter Doherty Institute for Infection and Immunity, University of Melbourne)

  • Gurdyal S. Besra

    (School of Biosciences, University of Birmingham)

  • Santosh Keshipeddy

    (University of Connecticut)

  • Stewart K. Richardson

    (University of Connecticut)

  • Amy R. Howell

    (University of Connecticut)

  • Stephanie Gras

    (Biomedicine Discovery Institute, Monash University
    Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University)

  • Dale I. Godfrey

    (Peter Doherty Institute for Infection and Immunity, University of Melbourne
    Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne)

  • Jamie Rossjohn

    (Biomedicine Discovery Institute, Monash University
    Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University
    Institute of Infection and Immunity, Cardiff University, School of Medicine)

  • Adam P. Uldrich

    (Peter Doherty Institute for Infection and Immunity, University of Melbourne
    Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne)

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.

Suggested Citation

  • 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 Gr, 2016. "Atypical natural killer T-cell receptor recognition of CD1d–lipid antigens," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10570
    DOI: 10.1038/ncomms10570
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