Antigen cross‐presentation: proteasome location, location, location

Our understanding of the mechanisms by which peptides from proteins present in phagosomes and endosomes are processed and presented on MHC class I molecules, in a pathway called cross‐presentation, is still incomplete. One of the main questions arising from currently proposed models is how do proteins in the phagosome lumen reach the proteasome in the cytoplasm to be processed properly. In this issue of The EMBO Journal , Sengupta et al (2019) present evidence for a surprising turn of events where, in fact, the proteasome acts within the lumen of endosomes and phagosomes. Graphical Abstract A new study shows that proteasomes in the lumen of phagosomes enable this organelle to process and present exogenous peptides on MHC class I molecules in the antigen cross‐presentation pathway.