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

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Le Nours, J; Praveena, T; Pellicci, DG; Gherardin, NA; Ross, FJ; Lim, RT; Besra, GS; Keshipeddy, S; Richardson, SK; Howell, AR; ...Date
2016-02-01Source Title
Nature CommunicationsPublisher
NATURE PUBLISHING GROUPUniversity of Melbourne Author/s
ROSS, FIONA; Godfrey, Dale; Uldrich, Adam; Pellicci, Daniel; Lim, Ratana; Gherardin, Nicholas; Rossjohn, JamieAffiliation
Microbiology and ImmunologyObstetrics and Gynaecology
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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 AccessAbstract
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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