Human CD1d molecules present an unknown ligand, mimicked by the synthetic glycosphingolipid α-galactosylceramide (αGC), to a highly conserved NKT cell subset expressing an invariant TCR Vα24-JαQ paired with Vβ11 chain (Vα24+ Vβ11+ invariant NK T cell (NKT inv)). The developmental pathway of Vα24+ Vβ11+ NKT inv is still unclear, but recent studies in mice were consistent with a TCR instructive, rather than a stochastic, model of differentiation. Using CD1d-αGC-tetramers, we demonstrate that in humans, TCR variable domains other than Vα24 and Vβ11 can mediate specific recognition of CD1d-αGC. In contrast to Vα24+ Vβ11+ NKT inv cells, Vα24−/CD1d-αGC-specific T cells express either CD8αβ or CD4 molecules, but they are never CD4 CD8 double negative. We show that CD8αβ+ Vα24−/CD1d-αGC-specific T cells exhibit CD8-dependent specific cytotoxicity and have lower affinity TCRs than Vα24+/CD1d-αGC-specific T cells. In conclusion, our results demonstrate that, contrary to the currently held view, recognition of CD1d-αGC complex in humans is not uniformly restricted to the Vα24-JαQ/Vβ11 NKT cell subset, but can be mediated by a diverse range of Vα and Vβ domains. The existence of a diverse repertoire of CD1d-αGC-specific T cells in humans strongly supports their Ag-driven selection.