The ER-SNARE Sec22b mediates the fusion between the ER and phagosomes and regulates cross presentation in dendritic cells

IGNACIO CEBRIAN; GÉRALDINE VISENTIN; NICOLAS BLANCHARD; CATARINA MOITA; LUIS F. MOITA; SEBASTIAN AMIGORENA; ARIEL SAVINA

Congreso; Congreso Anual del CFCD 2010; 2010

Cross presentation is the process by which exogenous antigens are processed and presented to the class I molecules of histocompatibility complex (MHC) to activate CD8+ T cells. Dendritic cells (DCs) have been shown to be the only antigen presenting cells that can perform efficiently antigen cross presentation, and this process has been involved in establishing cytotoxic immune responses against bacteria, tumors and certain virus that do not infect DCs. The presence of Endoplasmic Reticulum (ER) components in phagosomes has been proposed to be important for cross presentation. However, there is no evidence about the mechanism by which these components are recruited to the internalization pathway to encounter the antigens and whether the fusion between both compartments is absolutely required for cross presentation. We show here that the ER-SNARE Sec22b is a key player mediating the fusion between the ER membranes and phagosomes and controlling cross presentation in DCs. By knocking down Sec22b expression in DCs we observed that cross presentation of olvalbumin (OVA) coated beads, soluble OVA or OVA expressing Toxoplasma gondii was strongly inhibited while the classical MHC class II and endogenous MHC class I presentation pathways were not affected. We also observed that phagosomes fail to acquire ER components efficiently and that ER-deficient phagosomes acquire more rapidly lysosomal markers displaying a higher proteolytic activity than normal DC phagosomes. Our results suggest that the fusion of the ER to phagosomes is essential for cross presentation not only by contributing with the MHC class I presentation machinery but also by modifying phagosome functions that promote cross presentation.