CD1d-Restricted and TCR-Mediated Activation of V_α14 NKT Cells by Glycosylceramides

Natural killer T (NKT) lymphocytes express an invariant T cell antigen receptor (TCR) encoded by the V_α14 and J_α281 gene segments. A glycosylceramide-containing α-anomeric sugar with a longer fatty acyl chain (C₂₆) and sphingosine base (C₁₈) was identified as a ligand for this TCR. Glycosylceramide-mediated proliferative responses of V_α14 NKT cells were abrogated by treatment with chloroquine–concanamycin A or by monoclonal antibodies against CD1d/V_β8, CD40/CD40L, or B7/CTLA-4/CD28, but not by interference with the function of a transporter-associated protein. Thus, this lymphocyte shares distinct recognition systems with either T or NK cells.