CTLs (Cytotoxic T Lymphocytes) and NK (Natural Killer) cells are the key immune effectors that eradicate infected cells or tumors. To destroy these targets, CTLs and NK cells mostly use the granule exocytosis pathway, which releases perforin and Granzymes from cytolytic granules into the immunological synapse formed with the target. Granzyme-A and Granzyme-B, the most abundant Granzymes, are delivered to the target cell cytosol through perforin and independently induce cell death. Granzyme-B enters the target-cell cytosol by a poorly understood mechanism involving perforin. Granzyme-B induces apoptosis through Caspase-dependent and Caspase-independent mechanisms (Ref.1).
Granzyme-B is unique among serine proteases because, like cysteine protease Caspases, it cleaves after aspartic acid residues and thus activates Caspase-mediated apoptosis. It cleaves and activates the apical Caspase, [...]