Components of the cytoplasmic antigen processing pathway regulates indirect antigen presentation by MHC class II molecules (106.23)

Abstract Indirect presentation is a process in which MHC class II-positive antigen-presenting cells (APCs) acquire and present antigens expressed by class II-negative allografts, tumours or infected cells. It is generally assumed that similar cellular biochemical mechanisms underlie direct and indirect antigen presentation. This is because in both cases antigens are delivered to the endo/lysosomes for proteolytic processing for assembly of derived peptides with class II molecules and their subsequent display on the cell surface of antigen presenting cells. Remarkably, upon testing this assumption, we found that indirect presentation involved LMP2-dependent immunoproteasomes, indicating that the antigen had accessed the recipient APC’s cytosol. In this cytosol, TAP and ERAAP, but not tapasin, partially destroyed the antigens slated for indirect presentation. Because autophagy was not involved in returning the donated antigen from the cytosol to the endo/lysosome, a novel mechanism(s) is predicted to underlie cytosol to endo/lysosome antigen transport. How components of the cytosolic antigen-processing pathway regulate indirect class II-restricted antigen presentation and the mechanism(s) by which cytosolic antigens are returned to the endo/lysosomes will be presented.