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

Journal article

Human CD1d molecules present an unknown ligand, mimicked by the synthetic glycosphingolipid alpha-galactosylceramide (alphaGC), to a highly conserved NKT cell subset expressing an invariant TCR Valpha24-JalphaQ paired with Vbeta11 chain (Valpha24(+)Vbeta11(+) invariant NK T cell (NKT(inv))). The developmental pathway of Valpha24(+)Vbeta11(+)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-alphaGC-tetramers, we demonstrate that in humans, TCR variable domains other than Valpha24 and Vbeta11 can mediate specific recognition of CD1d-alphaGC. In contrast to Valpha24(+)Vbeta11(+)NKT(inv) cells, Valpha24(-)/CD1d-alphaGC-specific T cells express either CD8alphabeta or CD4 molecules, but they are never CD4 CD8 double negative. We show that CD8alphabeta(+)Valpha24(-)/CD1d-alphaGC-specific T cells exhibit CD8-dependent specific cytotoxicity and have lower affinity TCRs than Valpha24(+)/CD1d-alphaGC-specific T cells. In conclusion, our results demonstrate that, contrary to the currently held view, recognition of CD1d-alphaGC complex in humans is not uniformly restricted to the Valpha24-JalphaQ/Vbeta11 NKT cell subset, but can be mediated by a diverse range of Valpha and Vbeta domains. The existence of a diverse repertoire of CD1d-alphaGC-specific T cells in humans strongly supports their Ag-driven selection.

Authors: Gadola, S; Dulphy, N; Salio, M; Cerundolo, V

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 168
• Issue: 11
• Pages: 5514-5520
• Publication date: 2002-06-01
• DOI: 10.4049/jimmunol.168.11.5514
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: CD4-Positive T-Lymphocytes; Lectins, C-Type; Antigens, CD1; Antigens, CD1d; Receptors, Antigen, T-Cell, alpha-beta; NK Cell Lectin-Like Receptor Subfamily B; CD8-Positive T-Lymphocytes; Galactosylceramides; Humans; Antigens, Surface