Gzm B

Abstract

Granzyme B (gzm B) belongs to a family of six neutral serine proteases found exclusively in specialized granules of activated cytotoxic lymphocytes (CTLs), NK cells and lymphokine-activated killer (LAK) cells. Purified gzm B from NK granules has been shown to induce apoptosis of nucleated target cells following the polymerization of perforin in the target cell membrane. Mouse gzm B is an enzyme of 27–29 kDa, which has aspartic acid as its unique substrate site. CPP32 is an intracellular substrate for gzm B. This chapter presents a study in which no defects were detected in hematopoiesis and lymphoid development in gzm B–/– mice. T cell activation was intact since mutant lymphocytes were normally activated in response to ConA and IL-2, and in mixed lymphocyte cultures. While transcription of the gzm A gene was normal, dramatic reductions in the levels of mRNA for gzm B observed in LAK cells. gzm B is required in CTL, NK, and LAK cells for the rapid induction of DNA fragmentation in target cells. gzm B is required for the cleavage and activation of CPP32, an event associated with the induction of DNA fragmentation in target cells.