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Recognition of CD1d-sulfatide mediated by a type II natural killer T cell antigen receptor

Nature Immunology volume 13, pages 857–863 (2012)Cite this article

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Abstract

Natural killer T cells (NKT cells) are divided into type I and type II subsets on the basis of differences in their T cell antigen receptor (TCR) repertoire and CD1d-antigen specificity. Although the mode by which type I NKT cell TCRs recognize CD1d-antigen has been established, how type II NKT cell TCRs engage CD1d-antigen is unknown. Here we provide a basis for how a type II NKT cell TCR, XV19, recognized CD1d-sulfatide. The XV19 TCR bound orthogonally above the A′ pocket of CD1d, in contrast to the parallel docking of type I NKT cell TCRs over the F′ pocket of CD1d. At the XV19 TCR–CD1d-sulfatide interface, the TCRα and TCRβ chains sat centrally on CD1d, where the malleable CDR3 loops dominated interactions with CD1d-sulfatide. Accordingly, we highlight the diverse mechanisms by which NKT cell TCRs can bind CD1d and account for the distinct antigen specificity of type II NKT cells.

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Figure 1: Analysis of the binding of the XV19 TCR to CD1d-sulfatide.
Figure 2: Overview of the docking of the type II NKT cell TCR.
Figure 3: Contacts between the XV19 TCR and CD1d.
Figure 4: Sulfatide-mediated contacts between the XV19 TCR and CD1d.
Figure 5: Energetic determinants of type II NKT cell TCR–CD1d-antigen interactions.

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Acknowledgements

We thank the staff at the MX2 beamline of the Australian synchrotron for assistance with data collection and Monash Macromolecular Crystallisation Facility for crystallization experiments. Supported by the National Health and Medical Research Council of Australia (D.I.G. and J.R.), the Australian Research Council, the Cancer Council of Victoria, the US National Institutes of Health (AI090450 and AI092108 to L.G.), the Swedish Research Council (S.L.C.), the Swedish Cancer Society (S.L.C.) and Monash University (S.G. and J.R.).

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Author notes

  1. Thierry Mallevaey

    Present address: Present address: Department of Immunology, University of Toronto, Toronto, Canada.,

  2. Onisha Patel, Daniel G Pellicci and Stephanie Gras: These authors contributed equally to this work.

  3. Dale I Godfrey and Jamie Rossjohn: These authors jointly directed this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia

    Onisha Patel, Stephanie Gras, Maria L Sandoval-Romero, Andrew J Clarke, Jérôme Le Nours, Alex Theodossis & Jamie Rossjohn

  2. Department of Microbiology & Immunology, University of Melbourne, Parkville, Australia

    Daniel G Pellicci, Adam P Uldrich & Dale I Godfrey

  3. Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, Colorado, USA

    Thierry Mallevaey & Laurent Gapin

  4. Department of Microbiology and Immunology, Institute of Biomedicine, University of Goteborg, Goteborg, Sweden

    Susanna L Cardell

  5. Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK

    Jamie Rossjohn

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Contributions

O.P., D.G.P. and S.G. generated and analyzed data; M.L.S.-R., A.J.C., A.T., A.P.U., J.L.N., T.M. and L.G. generated data; S.L.C. provided the XV19 and VIII24 cells; and D.I.G. and J.R. together led the investigation, devised the project, analyzed the data and wrote the manuscript.

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Correspondence to Dale I Godfrey or Jamie Rossjohn.

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The authors declare no competing financial interests.

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Patel, O., Pellicci, D., Gras, S. et al. Recognition of CD1d-sulfatide mediated by a type II natural killer T cell antigen receptor. Nat Immunol 13, 857–863 (2012). https://doi.org/10.1038/ni.2372

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