Recognition of CD1d-sulfatide mediated by a type II natural killer T cell antigen receptor.
Research paper by
Onisha O Patel, Daniel G DG Pellicci, Stephanie S Gras, Maria L ML Sandoval-Romero, Adam P AP Uldrich, Thierry T Mallevaey, Andrew J AJ Clarke, Jérôme J Le Nours, Alex A Theodossis, Susanna L SL Cardell, Laurent L Gapin, Dale I DI Godfrey, Jamie J Rossjohn
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.