The primary mechanism by which cytotoxic T cells eliminate virally infected cells is by granule exocytosis. The release of cytotoxic granule contents by cytotoxic T lymphocytes (CTL) triggers apoptotic target cell death. CTL granules contain a pore-forming protein, perforin, and a group of serine proteases called granzymes. In the classic model, perforins create holes in the target cell membrane, allowing entrance of the granzymes. Granzyme A and B are the predominant granzymes activated after CTL activation, but each act via an independent apoptotic pathway; granzyme B is activated immediately, while granzyme A acts hours later. Granzyme B has been shown to induce apoptosis and to cleave a number of substrates which are similar in specificity to those of the caspase family of proteinases. Granzyme B can cleave substrates, such as DNA-PKcs, and nuclear mitotic apparatus protein (NuMA). Furthermore, Granzyme B can also cleave substrates such as Bid and DFF45 in a caspase-independent fashion. Studies involving mice which are deficient in both granzyme A and B suggest a model whereby the granzyme B pathway may have evolved as the major apoptotic pathway with the granzyme A pathway acting as a backup. However, further research is needed to delineate the components of these distinct pathways. Clone CB9 recognizes human granzyme A. Purified human granzyme A was used as the immunogen.
This antibody is routinely tested by flow cytometric analysis. Other applications were tested at BD Biosciences Pharmingen during antibody development only or reported in the literature.