Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Semin Immunol. 2023 Mar;66:101729. doi: 10.1016/j.smim.2023.101729. Epub 2023 Feb 16.
Phagocytes, particularly dendritic cells (DCs), generate peptide-major histocompatibility complex (MHC) I complexes from antigens they have collected from cells in tissues and report this information to CD8 T cells in a process called cross-presentation. This process allows CD8 T cells to detect, respond and eliminate abnormal cells, such as cancers or cells infected with viruses or intracellular microbes. In some settings, cross-presentation can help tolerize CD8 T cells to self-antigens. One of the principal ways that DCs acquire tissue antigens is by ingesting this material through phagocytosis. The resulting phagosomes are key hubs in the cross-presentation (XPT) process and in fact experimentally conferring the ability to phagocytize antigens can be sufficient to allow non-professional antigen presenting cells (APCs) to cross-present. Once in phagosomes, exogenous antigens can be cross-presented (XPTed) through three distinct pathways. There is a vacuolar pathway in which peptides are generated and then bind to MHC I molecules within the confines of the vacuole. Ingested exogenous antigens can also be exported from phagosomes to the cytosol upon vesicular rupture and/or possibly transport. Once in the cytosol, the antigen is degraded by the proteasome and the resulting oligopeptides can be transported to MHC I molecule in the endoplasmic reticulum (ER) (a phagosome-to-cytosol (P2C) pathway) or in phagosomes (a phagosome-to-cytosol-to-phagosome (P2C2P) pathway). Here we review how phagosomes acquire the necessary molecular components that support these three mechanisms and the contribution of these pathways. We describe what is known as well as the gaps in our understanding of these processes.
吞噬细胞，特别是树突状细胞 (DC)，从组织中细胞收集的抗原中生成肽-主要组织相容性复合物 (MHC) I 复合物，并在称为交叉呈递的过程中将此信息报告给 CD8 T 细胞。该过程使 CD8 T 细胞能够检测、响应和消除异常细胞，如癌症细胞或感染病毒或细胞内微生物的细胞。在某些情况下，交叉呈递可以帮助 CD8 T 细胞耐受自身抗原。DC 获得组织抗原的主要方式之一是通过吞噬作用摄取这种物质。由此产生的吞噬体是交叉呈递 (XPT) 过程的关键枢纽，事实上，实验中赋予吞噬抗原的能力足以使非专业抗原提呈细胞 (APC) 进行交叉呈递。一旦进入吞噬体，外源性抗原可通过三种不同途径进行交叉呈递 (XPTed)。存在一个液泡途径，其中肽生成，然后在液泡的限制内与 MHC I 分子结合。吞噬的外源性抗原也可以在囊泡破裂和/或可能运输时从吞噬体中输出到细胞质。一旦进入细胞质，抗原就会被蛋白酶体降解，产生的寡肽可以转运到内质网 (ER) 中的 MHC I 分子 (吞噬体到细胞质 (P2C) 途径) 或吞噬体中 (吞噬体到细胞质到吞噬体 (P2C2P) 途径)。在这里，我们回顾了吞噬体如何获得支持这三种机制的必要分子成分，以及这些途径的贡献。我们描述了已知的以及我们对这些过程理解的差距。
