Noncanonical use of the autophagy machinery in antigen presentation

The autophagy machinery has originally been described by Yoshinori Ohsumi as required for yeast to survive starvation periods. It consists of a series of kinase and membrane modification complexes that regulate membrane trafficking and substrate recruitment by covalently linking proteins of the LC3 family to lipids that then recruit cytoplasmic constituents for lysosomal degradation. This machinery is also utilized by other intracellular pathways such as endo- and exocytosis, including LC3-associated phagocytosis. Since these noncanonical uses of the autophagy machinery also influence the trafficking of antigens in infected and tumor cells, antigen presentation on MHC molecules that monitor intracellular degradation processes by presenting their peptide products is also affected. In this chapter, these autophagy-unrelated effects of ATG proteins on extracellular and intracellular antigen processing for MHC class I and II presentation will be discussed. In recent years it has become clear that the autophagy machinery supports both intracellular and extracellular antigen processing for MHC class II presentation to CD4⁺ T cells, while intracellular antigen presentation on MHC class I molecules is compromised by ATG proteins and some forms of extracellular antigen cross-presentation on MHC class I molecules benefit from them. In the future the mechanisms by which ATG proteins are distributed to these different pathways need to be characterized in order to manipulate the different antigen-processing pathways for MHC presentation and T cell stimulation.