PROCESSING AND ACTIVATION OF CMH-1 BY GRANZYME-B

Granzyme B plays an essential role in cytotoxic T lymphocyte (CTL)-med iated cell killing, Recent studies suggest that granzyme B may exert i ts effect by cleaving and activating CPP32, a member of the interleuki n-1 beta-converting enzyme/Ced-3 family of cysteine proteases, We have examined the processing and activation of CMH-1, a close homologue of CPP32, by granzyme B in vitro, We have found that granzyme B specific ally cleaves CMH-1 at Asp(198)-Ser(199) between the p20 and p12 and ac tivates the cysteine protease, Cleavage between p20 and the prosequenc e of CMH-1 at Asp(23)-Ala(24) is autocatalytic and is not required for CMH-1 activity in vitro. The cleavage and activation of CMH-1 by gran zyme B in vitro suggest that, in addition to CPP32, CMH-1 may also pla y a role in CTL-mediated cell killing.