Methods for Detecting Lytic Granules in Natural Killer Cells

Natural killer (NK) cells are able to identify and destroy target cells with absent or altered major histocomaptibility complex (MHC) class I, thereby mediating “natural cytotoxicity.” They also have the capacity to kill antibodycoated target cells by antibody-dependent cellular cytotoxicity (ADCC). The proteins that mediate these killing processes are stored in specialised secretory granules in the NK cells. When the NK cell recognizes its target these granules polarize toward the point of membrane contact and secrete their contents into the space between the cells. The major components of these granules are known (reviewed in ref. 1 ) and one of these proteins, perforin, inserts into the target cell membrane polymerizing to form a pore through which other proteins (granzymes) can pass and initiate cell death through the apoptotic pathway. Perforin alone can lyse the target cells by the formation of membrane pores although this process is relatively slow and it is likely that the granzymes are critical in effecting rapid cell death in vivo.