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

Jerome 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

Journal article

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

Jerome 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

NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2016

DOI: 10.1038/ncomms10570

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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 ..

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University of Melbourne Researchers

Dale Godfrey Author Microbiology and Immunology

Nicholas Gherardin Author Microbiology and Immunology

Adam Uldrich Author Microbiology and Immunology

Daniel Pellicci Author Microbiology and Immunology

Jamie Rossjohn Author Microbiology and Immunology

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Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by Cancer Council of Victoria the Australian Research Council (ARC)

Awarded by NIH

Awarded by NHMRC ECF fellowship

Awarded by NHMRC Senior Principal Research Fellowship

Awarded by NHMRC Australia Fellowship

Awarded by ARC Future Fellowships

Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

Funding Acknowledgements

We thank staff at the Australian synchrotron, the Monash macromolecular crystallization facility, Shin Yi Tin, John Waddington, Marcin Ciula and Ben O'Sullivan for technical assistance. We also thank Professors Paul Savage for providing a-GalCer (PBS44) and Lorenzo Moretta for providing anti-TRDV1 mAb. This work was supported by the National Health and Medical Research Council of Australia (NHMRC #1013667 and #1083885), The Cancer Council of Victoria the Australian Research Council (ARC) (CE140100011, LP140100920 and LE110100106) and the NIH RO1 GM087136 (to A.R.H.). D.G.P. is supported by an NHMRC ECF fellowship (#1054431); D.I.G. is supported by an NHMRC Senior Principal Research Fellowship (#1020770); J.R. is supported by an NHMRC Australia Fellowship (AF50); A.P.U. and S.G. are supported by an ARC Future Fellowships (FT140100278 and FT120100416).