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TY - JOUR AU - Le Nours, Jérôme AU - Praveena, T. AU - Pellicci, Daniel G. AU - Gherardin, Nicholas A. AU - Ross, Fiona J. AU - Lim, Ricky T. AU - Besra, Gurdyal S. AU - Keshipeddy, Santosh AU - Richardson, Stewart K. AU - Howell, Amy R. AU - Gras, Stephanie AU - Godfrey, Dale I. AU - Rossjohn, Jamie AU - Uldrich, Adam P. PY - 2016 DA - 2016/02/15 TI - Atypical natural killer T-cell receptor recognition of CD1d–lipid antigens JO - Nature Communications SP - 10570 VL - 7 IS - 1 AB - 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. SN - 2041-1723 UR - https://doi.org/10.1038/ncomms10570 DO - 10.1038/ncomms10570 ID - Le Nours2016 ER -