V 24-J Q-Independent, CD1d-Restricted Recognition of -Galactosylceramide by Human CD4 and CD8 T Lymphocytes

Human CD1d molecules present an unknown ligand, mimicked by the synthetic glycosphingolipid -galactosylceramide ( GC), to a highly conserved NKT cell subset expressing an invariant TCR V 24-J Q paired with V 11 chain (V 24 V 11 invariant NK T cell (NKT)). The developmental pathway of V 24 V 11 NKT is still unclear, but recent studies in mice were consistent with a TCR instructive, rather than a stochastic, model of differentiation. Using CD1dGC-tetramers, we demonstrate that in humans, TCR variable domains other than V 24 and V 11 can mediate specific recognition of CD1dGC. In contrast to V 24 V 11 NKT cells, V 24 /CD1dGC-specific T cells express either CD8 or CD4 molecules, but they are never CD4 CD8 double negative. We show that CD8 V 24 /CD1dGC-specific T cells exhibit CD8-dependent specific cytotoxicity and have lower affinity TCRs than V 24 /CD1dGC-specific T cells. In conclusion, our results demonstrate that, contrary to the currently held view, recognition of CD1dGC complex in humans is not uniformly restricted to the V 24-J Q/V 11 NKT cell subset, but can be mediated by a diverse range of V and V domains. The existence of a diverse repertoire of CD1dGC-specific T cells in humans strongly supports their Ag-driven selection. The Journal of Immunology, 2002, 168: 5514–5520.