The physiological role of immune shedding

Ectodomain shedding is a post-translational modification that regulates the expression levels of surface receptors and ligands. Natural killer (NK) cells are particularly sensitive to this process, because shedding modulates the magnitude of receptor engagement. Our laboratory has developed antibodies that inhibit ectodomain shedding in a substrate-specific manner, which enables physiologically relevant studies to establish a causal relationship between shedding inhibition and biological effects. These studies are revealing that the shedding of immune receptors and ligands homeostatically regulates NK cell-driven tumor immunity. Antibody-mediated inhibition of shedding is a novel niche in basic research and has potential for cancer immunotherapy.