Regulation of adaptive immunity by proteolytic systems.

Dendritic cells chew up bits of flu virus and other pathogens into smaller pieces, but the enzymes doing the cutting often destroy the very fragments needed to trigger a protective immune response. This project tackles a fundamental gap in immunology: how immune cells control the breakdown of foreign proteins inside their internal compartments. The researchers want to understand why some cuts happen too fast or in the wrong place, preventing the immune system from properly "seeing" a pathogen. They will study real dendritic cells from mice, not lab-grown cell lines, and focus on two key players: an unusually precise enzyme called asparagine endopeptidase (AEP) and a regulator called cystatin F that appears to control protease activity in killer T cells, natural killer cells, and other immune cells. If successful, this work could reveal how to redesign vaccines so that antigen fragments survive longer inside cells, giving the immune system a better chance to capture them. The researchers plan to test this by mutating cleavage sites in model antigens and vaccines to reduce unnecessary cuts. This is fundamental science—there is no immediate clinical application—but understanding how proteases shape immune responses could eventually lead to more effective vaccines against viruses that currently evade immunity, such as HIV or influenza.