nature20121129-3

墨尔本大学和莫纳什大学联合领导的研究首次为人们揭示了感染早期,黏膜相关恒定T 淋巴细胞(MAIT细胞)能够通过识别细菌和酵母的维生素B合成产物来激活免疫系统。

-2012年11月29日《自然》

中文翻译


【题目】 MR1呈递微生物维生素B代谢产物至MAIT细胞

【译文】 抗原呈递分子是由主要组织相容性复合物(MHC)和CD1家族编码的,它们分别结合基于多肽和脂质的抗原以被T细胞识别。粘膜相关恒定T淋巴细胞是人类中一类丰富的先天样T细胞,可被结合在I类MHC样分子MR1上的抗原所活化。尽管MR1限制的抗原的身份还不清楚,但它出现在大量细菌和酵母中。本研究表明MR1抗原结合裂缝中的结构和化学性质与MHC和CD1家族显著不同。MR1完美地适合于结合维生素代谢产生的配体。 MR1与6-甲酰基蝶呤(一种叶酸代谢产物)形成复合物的结构表明蝶呤环埋藏在MR1中。此外,我们还界定了相关MR1限制的维生素衍生物,它们来自于细菌核黄素生物合成途径,而核黄素可以特异性和潜在地激活MAIT细胞。相应地,本研究表明维生素B代谢产物代表了为MAIT细胞免疫监视而由MR1呈递的一类抗原。由于许多维生素生物合成途径是细菌和酵母所特有的,因此我们的数据表明MAIT细胞利用这些代谢产物以检测微生物感染。

英文原稿


[Title]: MR1 presents microbial vitamin B metabolites to MAIT cells

[Authors]:Lars Kjer-Nielsen,1 Onisha Patel,2 Alexandra J. Corbett,1 Jérôme Le Nours,2, 3 Bronwyn Meehan,1 Ligong Liu,4 Mugdha Bhati,2 Zhenjun Chen,1 Lyudmila Kostenko,1 Rangsima Reantragoon,1 Nicholas A. Williamson,5 Anthony W. Purcell,2, 5 Nadine L. Dudek,2, 5 Malcolm J. McConville,5 Richard A. J. O’Hair,6 George N. Khairallah,6 Dale I. Godfrey,1 David P. Fairlie,4 Jamie Rossjohn2, 3, 7, 8 & James McCluskey1, 8

[Abstract]Antigen-presenting molecules, encoded by the major histocompatibility complex (MHC) and CD1 family, bind peptide- and lipid-based antigens, respectively, for recognition by T cells. Mucosal-associated invariant T (MAIT) cells are an abundant population of innate-like T cells in humans that are activated by an antigen(s) bound to the MHC class I-like molecule MR1. Although the identity of MR1-restricted antigen(s) is unknown, it is present in numerous bacteria and yeast. Here we show that the structure and chemistry within the antigen-binding cleft of MR1 is distinct from the MHC and CD1 families. MR1 is ideally suited to bind ligands originating from vitamin metabolites. The structure of MR1 in complex with 6-formyl pterin, a folic acid (vitamin B9) metabolite, shows the pterin ring sequestered within MR1. Furthermore, we characterize related MR1-restricted vitamin derivatives, originating from the bacterial riboflavin (vitamin B2) biosynthetic pathway, which specifically and potently activate MAIT cells. Accordingly, we show that metabolites of vitamin B represent a class of antigen that are presented by MR1 for MAIT-cell immunosurveillance. As many vitamin biosynthetic pathways are unique to bacteria and yeast, our data suggest that MAIT cells use these metabolites to detect microbial infection.

原文地址

http://www.nature.com/nature/journal/v491/n7426/full/nature11605.html

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