The pathway, which has also been seen by Marianne Boes, Hidde Ploegh (Harvard Medical School, Boston, MA), and colleagues, starts at lysosomes, which in most cells are highly degradative. But in immature dendritic cells (DCs), lysosomes house internalized antigens and MHC class II molecules until the cells mature. After maturation, MHC II molecules reside on the plasma membrane, where they activate T cells. Previous microscopy of maturing DCs has given glimpses of tubulating lysosomes and nonlysosomal vesicles that contain MHC II molecules, hinting at the presence of an unusual transport pathway.
Chow et al. have now put the pathway together by combining conventional microscopy with total internal reflectance fluorescence microscopy, which can be used to visualize fusion events. Examining live DCs expressing GFP-labeled MHC II molecules, says Mellman, “we see that transporters can leave lysosomes and travel all the way to the cell surface carrying the cargo we expected.” Thus, MHC II molecules and their bound antigens end up on the plasma membrane instead of being degraded. Other cells may also be capable of retrograde transport from lysosomes, although it is most easily seen in maturing DCs because the process is synchronized. ▪