Redirecting soluble antigen for MHC class I cross-presentation during phagocytosis.

Redirecting soluble antigen for MHC class I cross-presentation during phagocytosis.
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吞噬过程中 MHC I 类交叉呈递的可溶性抗原的重定向

DOI:
10.1002/eji.201445156
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发表时间:
2015-02
影响因子:
5.4
通讯作者:
Shi, Yan
Shi, Yan
中科院分区:
医学3区
文献类型:
--
作者:
Hari, Aswin;Ganguly, Anutosh;Mu, Libing;Davis, Shevaun P.;Stenner, Melanie D.;Lam, Raymond;Munro, Fay;Namet, Inana;Alghamdi, Enaam;Fuerstenhaupt, Tobias;Dong, Wei;Detampel, Pascal;Shen, Lian Jun;Amrein, Matthias W.;Yates, Robin M.;Shi, Yan

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由MHC I类分子呈递的肽主要来源于由抗原呈递细胞自身合成的蛋白质,而由MHC II类分子呈递的肽主要来源于通过内吞作用获得的物质。外部抗原也可以在称为交叉呈递的过程中由MHC I类分子呈递。我们报告说,小鼠树突状细胞参与吞噬目标改变内吞加工,抑制其蛋白水解活性。在吞噬作用期间,内体成熟被延迟,向溶酶体的进展较少,并且内吞的可溶性抗原被靶向用于MHC I类交叉呈递。在这些被阻滞的内体中的抗原加工在与ROS相关的NAPDH氧化酶的控制下。我们还表明,组织蛋白酶S是负责的MHC I类表位的产生。我们的研究结果表明,除了固体结构摄取,DC吞噬作用同时修改内体运输和成熟的动力学。因此,外部可溶性抗原被靶向到MHC I类交叉呈递途径中。
Peptides presented by MHC class I molecules are derived mostly from proteins synthesized by the antigen-presenting cell itself, while peptides presented by MHC class II molecules are derived predominantly from materials acquired by endocytosis. External antigens can also be presented by MHC class I molecules in a process referred to as cross-presentation. We report that mouse dendritic cell engagement of a phagocytic target alters endocytic processing and inhibits their proteolytic activities. During phagocytosis, endosome maturation is delayed, shows less progression towards the lysosome, and the endocytosed soluble antigen is targeted for MHC class I cross-presentation. The antigen processing in these arrested endosomes is under the control of NAPDH oxidase associated ROS. We also show that cathepsin S is responsible for the generation of the MHC class I epitope. Our results suggest that in addition to solid structure uptake, DC phagocytosis simultaneously modifies the kinetics of endosomal trafficking and maturation. As a consequence, external soluble antigens are targeted into the MHC class I cross-presentation pathway.
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