Fig. 5.

Model of VAMP8-mediated antigen cross-presentation. (step 1) Uptake of antigen via endocytosis or phagocytosis. (2) Recruitment of cytochrome b₅₅₈ (Cyt b₅₅₈) to the antigen-containing compartment by VAMP8, SNAP23 and syntaxin-7. (3) The cytosolic subunits of NOX2 (NOX2_cyt; consisting of p40^phox, p47^phox and p67^phox) and the small GTPase Rac are recruited to cytochrome b₅₅₈. Fully assembled NOX2 on the phagosome produces ROS in the organellar lumen. (4) ROS lead to disruption of the phagosomal membrane allowing translocation of antigen into the cytosol. In the cytosol, the antigen becomes accessible for degradation by the proteasome. The proteasome-derived peptide fragments are imported in the endoplasmatic reticulum (ER) by the transporter associated with antigen processing (TAP) for loading onto MHC class I molecules (MHC-I). (5) The MHC:peptide complex is transported to the cell surface to cross-present the antigen to naive cytolytic T cells.