Blocking acid, boosting T cells

Intracellular antacids boost cytotoxic T cell responses, according to a study on page 817. Accapezzato and colleagues show that an inhibitor that prevents endosome acidification enhances presentation of antigens to CD8⁺ T cells and boosts vaccine responses.

Many vaccines are made of soluble proteins derived from viruses or bacteria. But these vaccines tend to be poor stimulators of CD8⁺ T cells, as soluble antigens are primarily degraded in acidified endosomes; the resulting peptides are loaded onto MHC class II molecules and presented to CD4⁺ helper T cells. But in certain cell types, exogenous antigen can escape from endosomes and enter the cytosol. From there, the antigen can infiltrate the class I MHC processing pathway—which is normally reserved for internally synthesized proteins—and be cross-presented to CD8⁺ T cells....