MHC I的途径进行外源性抗原的交叉呈递。
Pathways of MHC I cross-presentation of exogenous antigens.
发表日期:2023 Feb 16
作者:
Freidrich M Cruz, Amanda Chan, Kenneth L Rock
来源:
SEMINARS IN IMMUNOLOGY
摘要:
噬菌细胞,特别是树突状细胞(DCs),从细胞组织中收集的抗原中生成肽-主要组织相容性复合物(MHC)I复合物,并将这些信息报告给CD8 T细胞,这个过程称为交叉呈递。这个过程使CD8 T细胞能够检测、响应和消除异常细胞,比如癌细胞或感染病毒或细胞内微生物的细胞。在某些情况下,交叉呈递可以帮助耐受CD8 T细胞的自身抗原。DCs获取组织抗原的一个主要方式是通过吞噬作用摄取材料。由此产生的吞噬体是交叉呈递(XPT)过程的关键枢纽,实验上,赋予吞噬抗原的能力足以使非专业抗原呈递细胞(APCs)进行交叉呈递。一旦进入吞噬体,外源性抗原可以通过三种不同的途径进行交叉呈递(XPTed)。有一种泡状途径,其中肽被生成,然后在泡腔内与MHC I分子结合。吞噬的外源性抗原也可以通过高尔基小体破裂和/或转运从吞噬体排出到细胞质中。一旦进入细胞质,抗原会被蛋白酶体降解,生成的寡肽可以通过内质网中的MHC I分子(一个吞噬体到细胞质(P2C)途径)或吞噬体(一个吞噬体到细胞质到吞噬体(P2C2P)途径)进行运输。在这里,我们审查了吞噬体如何获得支持这些三种机制的必要分子组分及其贡献。我们描述了已知的情况以及我们对这些过程理解的差距。Copyright © 2023 Elsevier Ltd. All rights reserved.
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.Copyright © 2023 Elsevier Ltd. All rights reserved.