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

作者：Le Nours Jerome; Praveena T; Pellicci Daniel G; Gherardin Nicholas A; Ross Fiona J; Lim Ricky T; Besra Gurdyal S; Keshipeddy Santosh; Richardson Stewart K; Howell Amy R; Gras Stephanie; Godfrey Dale I^*; Rossjohn Jamie^*; Uldrich Adam P^*

来源：Nature Communications, 2016, 7(1): 10570.

DOI：10.1038/ncomms10570

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-alpha-galactosylceramide (alpha-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 alpha- and beta-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 alpha-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-alpha-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition.

• 出版日期2016-2