Münz Christian
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
Front Immunol. 2022 Mar 4;13:868888. doi: 10.3389/fimmu.2022.868888. eCollection 2022.
Macroautophagy delivers cytoplasmic constituents for lysosomal degradation. Since major histocompatibility complex (MHC) class II molecules sample peptides after lysosomal degradation for presentation to CD4 T cells, it was originally described that these peptides can also originate from macroautophagy substrates. In recent years it has become clear that in addition to this canonical function of the macroautophagy machinery during MHC class II restricted antigen presentation at least parts of this machinery are also used to regulate phagocytosis of antigens, degradation of MHC class I molecules, and unconventional secretion of antigens in extracellular vesicles, including virus particles. This review discusses how both canonical and non-canonical functions of the macroautophagy machinery influence antigen presentation on MHC class I and II molecules to CD8 and CD4 T cells. A better understanding of the molecular mechanisms by which the macroautophagy machinery is distributed between its canonical and non-canonical functions should allow targeting of antigens to these different pathways to influence MHC restricted presentation during vaccination against infectious diseases and tumors.
巨自噬将细胞质成分输送至溶酶体进行降解。由于主要组织相容性复合体（MHC）II类分子在溶酶体降解后对肽段进行采样，以呈递给CD4 T细胞，最初有研究表明这些肽段也可源自巨自噬底物。近年来，越来越清楚的是，除了巨自噬机制在MHC II类限制性抗原呈递过程中的这种经典功能外，该机制的至少部分功能还被用于调节抗原的吞噬作用、MHC I类分子的降解以及细胞外囊泡（包括病毒颗粒）中抗原的非常规分泌。本综述讨论了巨自噬机制的经典和非经典功能如何影响MHC I类和II类分子向CD8和CD4 T细胞呈递抗原。更好地理解巨自噬机制在其经典和非经典功能之间分配的分子机制，应该能够将抗原靶向这些不同途径，以在针对传染病和肿瘤的疫苗接种过程中影响MHC限制性呈递。
