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 () and Adam P. Uldrich ()
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Jérôme Le Nours: Biomedicine Discovery Institute, Monash University
T. Praveena: Biomedicine Discovery Institute, Monash University
Daniel G. Pellicci: Peter Doherty Institute for Infection and Immunity, University of Melbourne
Nicholas A. Gherardin: Peter Doherty Institute for Infection and Immunity, University of Melbourne
Fiona J. Ross: Peter Doherty Institute for Infection and Immunity, 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
Dale I. Godfrey: Peter Doherty Institute for Infection and Immunity, University of Melbourne
Jamie Rossjohn: Biomedicine Discovery Institute, Monash University
Adam P. Uldrich: Peter Doherty Institute for Infection and Immunity, University of Melbourne

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10570

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