Vα24-JαQ-independent, CD1d-restricted recognition of α-galactosylceramide by human CD4+ and CD8αβ+ T lymphocytes
Vα24-JαQ-independent, CD1d-restricted recognition of α-galactosylceramide by human CD4+ and CD8αβ+ T lymphocytes
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DOI：
10.4049/jimmunol.168.11.5514
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发表时间：
2002-06-01
影响因子：
4.4
通讯作者：
Cerundolo, V
中科院分区：
文献类型：
--
作者：
Gadola, SD;Dulphy, N;Cerundolo, V
Human CD1d molecules present an unknown ligand, mimicked by the synthetic glycosphingolipid a-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 (NKTinv)). 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.
