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Cross-presentation by intercellular peptide transfer through gap junctions

机译:通过间隙连接通过细胞间肽转移进行交叉展示

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摘要

Major histocompatibility complex (MHC) class I molecules present peptides that are derived from endogenous proteins1. These antigens can also be transferred to professional antigen-presenting cells in a process called cross-presentation, which precedes initiation of a proper T-cell response(2,3); but exactly how they do this is unclear. We tested whether peptides can be transferred directly from the cytoplasm of one cell into the cytoplasm of its neighbour through gap junctions. Here we show that peptides with a relative molecular mass of up to,1,800 diffuse intercellularly through gap junctions unless a three-dimensional structure is imposed. This intercellular peptide transfer causes cytotoxic T-cell recognition of adjacent, innocent bystander cells as well as activated monocytes. Gap-junction-mediated peptide transfer is restricted to a few coupling cells owing to the high cytosolic peptidase activity. We present a mechanism of antigen acquisition for cross-presentation that couples the antigen presentation system of two adjacent cells and is lost in most tumours: gap-junction-mediated intercellular peptide coupling for presentation by bystander MHC class I molecules and transfer to professional antigen presenting cells for cross-priming.
机译:主要的组织相容性复合体(MHC)I类分子呈现的肽类均来源于内源性蛋白质1。这些抗原也可以在称为交叉呈递的过程中转移到专业的抗原呈递细胞中,该过程先引发适当的T细胞反应(2,3)。但他们究竟如何做到这一点尚不清楚。我们测试了肽是否可以通过间隙连接直接从一种细胞的细胞质转移到其邻居的细胞质中。在这里我们显示,除非施加三维结构,否则相对分子质量最高为1,800的肽会通过间隙连接在细胞内扩散。这种细胞间肽转移导致相邻无辜旁观者细胞以及活化的单核细胞的细胞毒性T细胞识别。由于高的胞质肽酶活性,间隙连接介导的肽转移仅限于少数偶联细胞。我们提出了一种交叉呈递的抗原获取机制,该机制耦合了两个相邻细胞的抗原呈递系统,并且在大多数肿瘤中丢失:间隙连接介导的细胞间肽偶联,由旁观者MHC I类分子呈递并转移至专业抗原呈递交叉启动细胞。

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