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

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    Author
    Le Nours, J; Praveena, T; Pellicci, DG; Gherardin, NA; Ross, FJ; Lim, RT; Besra, GS; Keshipeddy, S; Richardson, SK; Howell, AR; ...
    Date
    2016-02-01
    Source Title
    Nature Communications
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    ROSS, FIONA; Godfrey, Dale; Uldrich, Adam; Pellicci, Daniel; Lim, Ratana; Gherardin, Nicholas; Rossjohn, Jamie
    Affiliation
    Microbiology and Immunology
    Obstetrics and Gynaecology
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    Document Type
    Journal Article
    Citations
    Le Nours, J., Praveena, T., Pellicci, D. G., Gherardin, N. A., Ross, F. J., Lim, R. T., Besra, G. S., Keshipeddy, S., Richardson, S. K., Howell, A. R., Gras, S., Godfrey, D. I., Rossjohn, J. & Uldrich, A. P. (2016). Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens. NATURE COMMUNICATIONS, 7 (1), https://doi.org/10.1038/ncomms10570.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/258398
    DOI
    10.1038/ncomms10570
    NHMRC Grant code
    NHMRC/1054431
    NHMRC/1020770
    NHMRC/1013667
    NHMRC/1083885
    ARC Grant code
    ARC/FT140100278
    ARC/LE110100106
    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.

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