The cross-presentation of exogenous peptides is necessary for priming efficient antiviral and antitumor immune responses. Specific dendritic cell subsets specialize in cross-presentation, but how this process allows antigen processing and loading of antigen onto major histocompatibility complex class I molecules remains unclear. In Cell, Cebrian et al. show that phagosomes in dendritic cells fuse with endoplasmic reticulum–Golgi transport vesicles via a fusogenic SNARE complex composed of Sec22b and syntaxin 4. Sec22b is located on the membranes of transport vesicles that move cargo between the endoplasmic reticulum and cis-Golgi compartments and can capture syntaxin 4 present on phagosomes, which allows mixing of membrane proteins, including peptide-loading machinery dependent on the transporter TAP. Cells that lack Sec22b fail to cross-present antigen to CD8+ T cells, which demonstrates the requirement for endoplasmic reticulum–phagosome vesicle fusion in this antigen-presentation process. How this Sec22b-dependent intracellular trafficking is regulated is unknown.

Cell 147, 1355–1368 (2011)