PROCESSING, SUBCELLULAR-LOCALIZATION, AND FUNCTION OF 519-(GRANULYSIN), A HUMAN LATE T-CELL ACTIVATION MOLECULE WITH HOMOLOGY TO SMALL, LYTIC, GRANULE PROTEINS

CTL and NK cells share a common cytolytic mechanism that involves regu lated exocytosis of lytic molecules stored within cytoplasmic granules . Here we describe the processing, subcellular localization, and funct ion of a T and NK cell-specific granule protein that shares homology w ith small, lytic granule-associated molecules. The gene coding for thi s protein, 519, is expressed late after T cell activation. Antisera ra ised against a 519/glutathione-S-transferase fusion protein and a seri es of peptides derived from the 519 protein sequence permitted the ide ntification of two small CTL protein products of 15 and 9 kDa that are exocytosed after stimulation through the TCR. The 9-kDa product is a processed form of 519 and differs from the 15-kDa product in both its amino and carboxyl terminus. While both 519 proteins are found in cyto plasmic granules, the 9-kDa form is also present in dense, highly cyto lytic granules. Functional studies indicate that this protein is lytic against tumor cell targets. The cell type- and stage-specific express ion pattern of 519 along with its subcellular localization are reminis cent of molecules that play a vital role in granule-mediated cytolysis by CTL and NK cells. Its lytic activity suggests the involvement of 5 19 in CTL effector function.