Autophagy in Antigen Processing for MHC Presentation to T Cells

T cells recognize infected tissues via the display of small protein fragments that are bound to major histocompatibility complex (MHC) molecules. These peptides are generated by the cellular proteolytic machineries, primarily proteasomes and lysosomes. Proteasomal products are primarily presented on MHC class I molecules to cytotoxic CD8⁺ T cells and lysosomal products primarily on MHC class II molecules to helper CD4⁺ T cells. Autophagy encompasses at least three pathways, by which cytoplasmic material is transported to lysosomes for degradation. These pathways, therefore, allow cytoplasmic antigens to be presented on MHC class II molecules. However, in recent years additional functions of the molecular machinery for one of these pathways, macroautophagy, have been shown to regulate other membrane transport mechanisms, influencing antigen phagocytosis and exocytosis. In addition, vesicular loading of MHC class I molecules, which usually bind proteasomal products in the endoplasmic reticulum, might benefit from macroautophagy. We will discuss these different pathways and their possible contribution to autoimmunity, some of which are genetically linked with macroautophagy. Modulation of these vesicular transport functions in order to regulate cell intrinsic, beneficial effects of autophagy, for example in cancer and neurodegeneration, should consider the discussed effects on immune regulation.