Granulysin, a new human cytolytic granule-associated protein with possible involvement in cell-mediated cytotoxicity

Abstract

A primary process by which cytotoxic T lymphocytes (CTL) and natural killer (NK) cells lyse target cells involves the regulated exocytosis of granules present in the cytoplasm of the effector. These granules contain proteins, such as perforin and the granzymes, that play a direct role in the killing profess. The localization of a human T and NK cell-specific protein, granulysin (formerly 519), to cytolytic granules suggests that additional mechanisms may be involved in granule-mediated cytolysis. This protein shares homology with small, granule-associated molecules and is a member of a larger family of proteins known as saposin-like proteins (SAPLIP). SAPLIP share common structural features allowing for association with lipids while retaining the ability to mediate a variety of different functions. Expression of granulysin is induced late after T-cell activation, similar to perforin and the granzymes. Two prominent protein products of 15 and 9 kDa were identified in CTL. The 9 kDa form localizes to dense, highly cytolytic granules and contains the SAPLIP homology domain. A recombinant granulysin protein, corresponding to the 9 kDa form, is cytolytic against tumor cell targets.