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Background
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Peptide substrate labeled at the carboxy end with AFC (7-amino-4-trifluoromethyl coumarin). Designed to measure Granzyme B activity in vitro. Cell-mediated killing by cytotoxic T-lymphocytes (CTLs) is an important immunologic defense against tumor cell proliferation, viral infection, and transplanted tissue. Cell death induced by CTLs is mostly apoptotic and is thought to involve perforin, a pore-forming protein, and the granzymes, a family of serine proteinases, that are present in the cytoplasmic granules of CTLs and natural killer (NK) cells. Seven serine proteases (Granzyme A, B, C, D, E, F, and G) have been isolated from mouse CTL granules. Two serine proteases (Granzyme A and B) have been isolated from human CTL granules and are homologous to the mouse enzymes. Granzyme B is the granzyme most specifically found in CTLs and the granzyme shown to cause the most rapid kinetics of cell death. Granzyme B shares an unusual substrate specificity with interleukin-1beta converting enzyme (ICE), another enzyme involved in apoptosis, in that both require an Asp in the P1 position.
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