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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 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.

Type

Journal article

Journal

Journal of Immunology

Publication Date

01/06/2002

Volume

168

Pages

5514 - 5520