The identification of the endogenous ligands of natural killer T cells reveals the presence of mammalian α-linked glycosylceramides.
The identification of the endogenous ligands of natural killer T cells reveals the presence of mammalian α-linked glycosylceramides.
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DOI：
10.1016/j.immuni.2014.08.017
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发表时间：
2014-10-16
期刊：
影响因子：
32.4
通讯作者：
Teyton, Luc
中科院分区：
文献类型：
--
作者：
Kain, Lisa;Webb, Bill;Anderson, Brian L.;Deng, Shenglou;Holt, Marie;Costanzo, Anne;Zhao, Meng;Self, Kevin;Teyton, Anais;Everett, Chris;Kronenberg, Mitchell;Zajonc, Dirk M.;Bendelac, Albert;Savage, Paul B.;Teyton, Luc
认为哺乳动物物种中的糖基神经酰胺以β-端基异构体的形式存在。在哺乳动物基因组中仅鉴定出一种葡糖神经酰胺合酶和一种半乳糖神经酰胺合酶（均为β-转移酶），进一步证实了这一结论。因此，少量α-端基异构体可能通过替代酶促途径、通过不忠实的酶或在不寻常的细胞区室中自发产生的可能性尚未详细研究。我们利用T和B淋巴细胞的特异性，并结合鞘脂途径分解代谢酶的特异性来解决这个问题。在这里，我们证明哺乳动物免疫细胞在组成上产生非常少量的α-糖基神经酰胺，它们是自然杀伤T细胞的主要内源性配体。神经酰胺和糖脂途径的分解代谢酶严格控制这些α-糖基神经酰胺的量。利用这一途径来操纵免疫反应将创造新的治疗机会。
Glycosylceramides in mammalian species are thought to be present in the form of β-anomers. This conclusion was reinforced by the identification of only one glucosylceramide and one galactosylcerhamide synthase, both β-transferases, in mammalian genomes. Thus, the possibility that small amounts of α-anomers could be produced by an alternative enzymatic pathway, by an unfaithful enzyme, or spontaneously in unusual cellular compartments has not been examined in detail. We approached the question by taking advantage of the exquisite specificity of T and B lymphocytes and combined it with the specificity of catabolic enzymes of the sphingolipid pathway. Here, we demonstrate that mammalian immune cells produce constitutively very small quantities of α-glycosylceramides, which are the major endogenous ligands of natural killer T cells. Catabolic enzymes of the ceramide and glycolipid pathway tightly control the amount of these α-glycosylceramides. The exploitation of this pathway to manipulate the immune response will create new therapeutic opportunities.
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影响因子：
30.5
作者：
Facciotti, Federica;Ramanjaneyulu, Gundimeda S.;De Libero, Gennaro
通讯作者：
De Libero, Gennaro
影响因子：
4.8
作者：
Eliyahu, Efrat;Park, Jae-Ho;Schuchman, Edward H.
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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。
影响因子：
30.5
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.
通讯作者：
Brenner, Michael B.
影响因子：
56.9
作者：
Meissner, Felix;Scheltema, Richard A.;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
4.4
作者：
Berzins, Stuart P.;McNab, Finlay W.;Godfrey, Dale I.
通讯作者：
Godfrey, Dale I.