CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution.
CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution.
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DOI：
10.1084/jem.188.8.1521
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发表时间：
1998-10-19
影响因子：
15.3
通讯作者：
Kronenberg, M
中科院分区：
文献类型：
--
作者：
Brossay, L;Chioda, M;Burdin, N;Koezuka, Y;Casorati, G;Dellabona, P;Kronenberg, M
自然杀伤（NK） T细胞是一种淋巴细胞亚群，具有独特的表面表型、不变性T细胞受体（TCR）和对CD1的反应性。在这里，我们发现小鼠NK T细胞可以识别人类CD1d和小鼠CD1，人类NK T细胞也可以识别这两种CD1同源物。这种T细胞识别系统前所未有的保护程度表明，它从根本上是重要的。小鼠或人CD1分子可以将糖脂α-半乳糖神经酰胺（α-GalCer）呈递给NK T细胞。预先选择Vα24 TCR表达不变的人T细胞，可以统一识别人CD1d或小鼠CD1呈递的α-GalCer。此外，用α-GalCer培养人外周血细胞，导致具有不变（v - α24+） TCR的NK T细胞急剧扩增，并释放大量细胞因子。由于不变的Vα14+和Vα24+ NK T细胞与自身免疫性疾病和肿瘤反应的控制有关，我们的数据表明α-GalCer可能是通过激活高度保守的NK T细胞亚群来调节人类免疫反应的有用药物。
Natural killer (NK) T cells are a lymphocyte subset with a distinct surface phenotype, an invariant T cell receptor (TCR), and reactivity to CD1. Here we show that mouse NK T cells can recognize human CD1d as well as mouse CD1, and human NK T cells also recognize both CD1 homologues. The unprecedented degree of conservation of this T cell recognition system suggests that it is fundamentally important. Mouse or human CD1 molecules can present the glycolipid α-galactosylceramide (α-GalCer) to NK T cells from either species. Human T cells, preselected for invariant Vα24 TCR expression, uniformly recognize α-GalCer presented by either human CD1d or mouse CD1. In addition, culture of human peripheral blood cells with α-GalCer led to the dramatic expansion of NK T cells with an invariant (Vα24+) TCR and the release of large amounts of cytokines. Because invariant Vα14+ and Vα24+ NK T cells have been implicated both in the control of autoimmune disease and the response to tumors, our data suggest that α-GalCer could be a useful agent for modulating human immune responses by activation of the highly conserved NK T cell subset.