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

Nature Immunology volume 13, pages 857863 (2012) | Download Citation


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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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

    • Thierry Mallevaey

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

    • Onisha Patel
    • , Daniel G Pellicci
    •  & Stephanie Gras

    These authors contributed equally to this work.

    • Dale I Godfrey
    •  & Jamie Rossjohn

    These authors jointly directed this work.


  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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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.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Dale I Godfrey or Jamie Rossjohn.

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