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T cells of the adaptive immune system monitor protein degradation products via their presentation on major histocompatibility complex (MHC) molecules to recognize infected cells. Both macroautophagy and endocytosis target intra- and extracellular constituents, respectively, for lysosomal degradation. This results in antigen processing for MHC presentation and influences the trafficking of MHC molecules. This review will discuss recent evidence that the molecular machinery of macroautophagy regulates also endocytosis at the level of phagosome maturation and cell membrane internalization. These non-canonical functions of this machinery affect both MHC class I and II restricted antigen presentation to CD8 and CD4 T cells, respectively, and should be harnessed to improve immune responses against infectious diseases and cancer.
This article was published in the following journal.
Name: Seminars in cancer biology
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Class I-restricted activation of CD8-POSITIVE LYMPHOCYTES resulting from ANTIGEN PRESENTATION of exogenous ANTIGENS (cross-presentation). This is in contrast to normal activation of these lymphocytes (direct-priming) which results from presentation of endogenous antigens.
The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)
An autophagy related protein which functions as a core subunit of PHOSPHATIDYLINOSITOL 3-KINASE MULTIPROTEIN COMPLEXES. It mediates the formation of phosphatidylinositol 3-phosphate and functions in AUTOPHAGY, where it is required for maturation of the AUTOPHAGOSOME. It also functions in ENDOCYTOSIS and CYTOKINESIS as part of a separate complex. Beclin-1 associates with INTRACELLULAR MEMBRANES and interacts with the PROTO-ONCOGENE PROTEINS C-BCL-2 and BCL-X PROTEIN.
Proteins and enzymes that function, often as components of MULTIPROTEIN COMPLEXES, to assemble AUTOPHAGOSOMES and carry out AUTOPHAGY.
An autophagy related protein that is similar to UBIQUITIN-ACTIVATING ENZYME E1. It functions in CYTOPLASM to VACUOLE transport (Cvt) and AUTOPHAGY by activating ATG12 PROTEIN for its conjugation with ATG5 PROTEIN, as well as the conjugation of ATG8 FAMILY PROTEINS with phosphatidylethanolamine for ATG8 association to Cvt vesicles and AUTOPHAGOSOME membranes. It is also required for the nitrogen starvation response in yeast, MITOPHAGY; and autophagic cell death induced by CASPASE 8 inhibition.