Journal article

CD1d-lipid antigen recognition by the gamma delta TCR

Adam P Uldrich, Jerome Le Nours, Daniel G Pellicci, Nicholas A Gherardin, Kirsty G McPherson, Ricky T Lim, Onisha Patel, Travis Beddoe, Stephanie Gras, Jamie Rossjohn, Dale I Godfrey



The T cell repertoire comprises αβ and γδ T cell lineages. Although it is established how αβ T cell antigen receptors (TCRs) interact with antigen presented by antigen-presenting molecules, this is unknown for γδ TCRs. We describe a population of human Vδ1(+) γδ T cells that exhibit autoreactivity to CD1d and provide a molecular basis for how a γδ TCR binds CD1d-α-galactosylceramide (α-GalCer). The γδ TCR docked orthogonally, over the A' pocket of CD1d, in which the Vδ1-chain, and in particular the germ line-encoded CDR1δ loop, dominated interactions with CD1d. The TCR γ-chain sat peripherally to the interface, with the CDR3γ loop representing the principal determinant for α-GalCer specifici..

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Funding Acknowledgements

We thank the staff at the MX1 and MX2 beamlines of the Australian Synchrotron for assistance with data collection, M. Sandoval, M. Ciula, D. Littler, R. Berry, J. Waddington, P. Neeson and D. Ritchie for technical assistance, provision of reagents and/or advice, staff from the flow cytometry facilities in the Melbourne Brain Centre and the Department of Microbiology and Immunology at The University of Melbourne and D. Maksel from the Macromolecular Crystallization Facility at Monash University for technical assistance, P. Savage (Brigham Young University) for providing PBS44 glycolipid, G. Besra (University of Birmingham, UK) and S. Porcelli (Albert Einstein College of Medicine) for providing alpha-glucosylceramide and the alpha-GalCer analog OCH, and D. Vignali (St. Jude Children's Research Hospital) and S. Turner (The University of Melbourne) for providing pMIG expression vector. This work was supported by the Australian Research Council and the National Health and Medical Research Council of Australia (NHMRC). N.A.G. is supported by a Leukaemia Foundation of Australia Postgraduate Scholarship; T. B. is supported by a Pfizer Australia Fellowship; S. G. and O.P. are supported by Australian Research Council Future Fellowships; D. G. P. is supported by an NHMRC Peter Doherty Fellowship; J.R. is supported by an NHMRC Australia Fellowship; D. I. G. is supported by an NHMRC Senior Principal Research Fellowship.