The endocytic pathway as a key modulator of antigen cross-presentation by dendritic cells

CEBRIAN, I; CROCE, C; DINAMARCA, S; BLANCHARD, N; MAYORGA LS

Parana

Congreso; SAIB 2018; 2018

SAIB

Cross-presentation by MHC class I molecules allows the detection of exogenous antigens by CD8+ T lymphocytes. This process is determinantto initiate cytotoxic immune responses against many pathogens (i.e. Toxoplasma gondii) and tumors. To achieve efficient cross-presentation,dendritic cells (DCs) have developed highly specialized adaptations of their endocytic network. Consequently, DCs are the most potent antigenpresenting cell type to accomplish this immunological process. However, a complete view of the many molecular effectors involved in antigencross-presentation is still missing. We have recently shown that the small GTPase Rab22a regulates the transport of MHC-I in DCs bystabilizing the intracellular pool of these molecules at the recycling center, allowing the normal delivery to phagosomes and guaranteeing anefficient recycling to the cell surface. Furthermore, we demonstrated that Rab22a modulates the acquisition of ER-derived proteins to endosomesbut not to phagosomes in DCs. All these intracellular trafficking defects that take place in Rab22a deficient DCs drive to a significantimpairment of antigen cross-presentation, including soluble, particulate and T. gondii-associated antigens. Recently, we have also started tostudy the role of sorting nexin (SNX) proteins during antigen cross-presentation. SNXs are characterized by the presence of a phox-homologydomain that interacts with elements of the endocytic pathway enriched with phosphatidylinositol-3-monophosphate. In this way, SNXs controlkey features of endocytosis, as well as endosomal signaling, sorting and tubulation. In particular, SNX17 associates with compartments of theearly endocytic network and participates in several processes of intracellular recycling. We have identified SNX17 as a main regulator of antigeninternalization and cross-presentation by DCs. Our findings provide compelling evidence that Rab22a and SNX17 play central roles in theendocytic transport of DCs and are crucial molecules to guarantee an efficient antigen cross-presentation.