Valpha24-JalphaQ-independent, CD1d-restricted recognition of alpha-galactosylceramide by human CD4(+) and CD8alphabeta(+) T lymphocytes

Gadola, Stephan D., Dulphy, Nicolas, Salio, Mariolina and Cerundolo, Vincenzo (2002) Valpha24-JalphaQ-independent, CD1d-restricted recognition of alpha-galactosylceramide by human CD4(+) and CD8alphabeta(+) T lymphocytes. Journal of Immunology, 168, 5514-5520. (PMID:12023346)

Abstract

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 V24-JQ paired with V11 chain (V24+V11+ invariant NK T cell (NKTinv)). The developmental pathway of V24+V11+NKTinv is still unclear, but recent studies in mice were consistent with a TCR instructive, rather than a stochastic, model of differentiation. Using CD1d-GC-tetramers, we demonstrate that in humans, TCR variable domains other than V24 and V11 can mediate specific recognition of CD1d-GC. In contrast to V24+V11+NKTinv cells, V24-/CD1d-GC-specific T cells express either CD8 or CD4 molecules, but they are never CD4 CD8 double negative. We show that CD8+V24-/CD1d-GC-specific T cells exhibit CD8-dependent specific cytotoxicity and have lower affinity TCRs than V24+/CD1d-GC-specific T cells. In conclusion, our results demonstrate that, contrary to the currently held view, recognition of CD1d-GC complex in humans is not uniformly restricted to the V24-JQ/V11 NKT cell subset, but can be mediated by a diverse range of V and V domains. The existence of a diverse repertoire of CD1d-GC-specific T cells in humans strongly supports their Ag-driven selection.

This record has no associated files available for download.

Contributors

Download statistics