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Regulation of the Cell Biology of Antigen Cross Presentation

机译:抗原交叉呈递的细胞生物学调控

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摘要

Antigen cross-presentation is an adaptation of the cellular process of loading MHC-I molecules with endogenous peptides during their biosynthesis within the endoplasmic reticulum. Cross-presented peptides derive from internalized proteins, microbial pathogens, and transformed or dying cells. The physical separation of internalized cargo from the endoplasmic reticulum, where the machinery for assembling peptide–MHC-I complexes resides, poses a challenge. To solve this problem, deliberate rewiring of organelle communication within cells is necessary to prepare for cross-presentation, and different endocytic receptors and vesicular traffic patterns customize the emergent cross-presentation compartment to the nature of the peptide source. Three distinct pathways of vesicular traffic converge to form the ideal cross-presentation compartment, each regulated differently to supply a unique component that enables cross-presentation of a diverse repertoire of peptides. Delivery of centerpiece MHC-I molecules is the critical step regulated by microbe-sensitive Toll-like receptors. Defining the subcellular sources of MHC-I and identifying sites of peptide loading during cross-presentation remain key challenges.
机译:抗原交叉呈递是在内质网内生物合成过程中向MHC-1分子内源性肽加载过程的适应。交叉呈递的肽源于内在化的蛋白质,微生物病原体以及转化或垂死的细胞。将内部化的货物与内质网物理分离,这是组装肽-MHC-1复合物的机械所在的地方,这是一个挑战。为了解决这个问题,有必要重新安排细胞内细胞器通讯的连线,以准备进行交叉展示,并且不同的内吞受体和囊泡运输方式可根据肽源的性质定制出现的交叉展示区室。三种不同的囊泡运输途径汇聚在一起,形成理想的交叉提呈区室,每个通道均受到不同的调节以提供独特的成分,从而能够交叉提呈多种肽类。核心MHC-1分子的传递是微生物敏感的Toll样受体调节的关键步骤。定义MHC-1的亚细胞来源并在交叉展示期间鉴定肽负载位点仍然是关键挑战。

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