Cell
Volume 49, Issue 5, 5 June 1987, Pages 679-685
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Article
A family of serine esterases in lytic granules of cytolytic T lymphocytes

https://doi.org/10.1016/0092-8674(87)90544-7Get rights and content

Abstract

Cytoplasmic granules of cytolytic T lymphocytes (CTLs) contain, in addition to the pore-forming protein perforin, a family of highly homologous serine esterases, granzymes A-H. The serine esterase affinity label diisopropyl fluorophosphate reacts strongly with granzymes A and D, to a lesser extent with B, E, F, G, and H, and not at all with C and F. For granzymes A and D, synthetic substrates have been found. Antibodies raised against granzyme B strongly cross-react with A, G, and H, and antibodies to granzyme D recognize C, E, and F. These antigenic relationships correlate with similarities in the N-terminal amino acid sequences. At least 60% homology is observed between the eight proteins, and all are similar to rat mast cell protease 2. Sequence analysis suggests the identity of granzyme A with a protease predicted from a CTL-specific cDNA clone (H factor) and of granzyme B, G, or H with a protein encoded by the CTL-specific cDNA clone CTLA 1/CCP 1.

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      Once in the synaptic cleft, perforin facilitates the entry of granzyme serine proteases into the cytosol of the target cell [7–19]. There are five humans granzymes (A, B, H, K, and M) and 10 mouse orthologs (A, B, C, D, E, F, G, K, M and N) [20–22]. The granzyme A (GA) and granzyme B (GB) apoptotic cascades are the best characterized [20–22].

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