Invariant natural killer T cells recognize lipid self antigen induced by microbial danger signals.

Invariant natural killer T cells recognize lipid self antigen induced by microbial danger signals.
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不变的天然杀手T细胞识别微生物危险信号引起的脂质自抗原。

DOI:
10.1038/ni.2143
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发表时间:
2011-10-30
期刊:
影响因子:
30.5
通讯作者:
Brenner, Michael B.
Brenner, Michael B.
中科院分区:
医学1区
文献类型:
--
作者:
Brennan, Patrick J.;Tatituri, Raju V. V.;Brigl, Manfred;Kim, Edy Y.;Tuli, Amit;Sanderson, Joseph P.;Gadola, Stephan D.;Hsu, Fong-Fu;Besra, Gurdyal S.;Brenner, Michael B.

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不变自然杀伤T细胞(iNKT细胞)在感染及其他炎症过程中发挥着重要作用,这些细胞可通过其T细胞受体被微生物脂质抗原激活。然而,越来越多的证据表明,在没有外来脂质抗原存在的情况下它们也会被激活,这提示了脂质自身抗原的作用。我们现在证明,一种丰富的内源性脂质,β - D - 吡喃葡萄糖苷神经酰胺(β - GlcCer),在小鼠和人类中是一种有效的iNKT细胞自身抗原,并且其活性取决于N - 酰基链的组成。此外,β - GlcCer在感染过程中以及在对Toll样受体激动剂作出反应时会积累,这有助于iNKT细胞的激活。因此,我们提出不变T细胞受体对β - GlcCer的识别将先天性危险信号转化为iNKT细胞的激活。
Invariant natural killer T cells (iNKT cells) play a prominent role during infection and other inflammatory processes, and these cells can be activated through their T cell receptors by microbial lipid antigens. However, increasing evidence shows that they are also activated in situations where no foreign lipid antigens are present, suggesting a role for lipid self-antigen. We now demonstrate that an abundant endogenous lipid, β-D-glucopyranosylceramide (β-GlcCer), is a potent iNKT cell self-antigen in mouse and human, and that its activity depends on N-acyl chain composition. Furthermore, β-GlcCer accumulates during infection and in response to Toll-like receptor agonists, contributing to iNKT cell activation. Thus, we propose that recognition of β-GlcCer by the invariant TCR translates innate danger signals into iNKT cell activation.
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