Specific cleavage sites on human IgG subclasses by cruzipain, the major cysteine proteinase from Trypanosoma cruzi.

摘要: Cruzipain, the major cysteine proteinase of Trypanosoma cruzi, might have other biological roles than its metabolic functions. In this report, we explored interaction cruzipain with molecules immune system. The enzyme was used to digest all human IgG subclasses at different pH values and lengths time. At 7.3, were readily split hinge region. Immunoblot amino acid sequence analysis showed fragments IgG1 IgG3 be compatible Fab Fc, whereas IgG2 IgG4 rendered Fab2 Fc. cases produced impair binding capacities effector functions specific IgG. these cleavage sites displays cathepsin L and/or B activities shows a clear preference for Pro P'2 position polar residues P1. Despite activity within hinge, also cleaved heavy chains between CH2 CH3 domains; producing Fc'-like-fragments 14 kDa. These are potential candidates block or saturate Fc receptors on immunocompetent cells. mild acidic further degradation subclasses, Fd partially IgG1, consistent loss any antibody activity. apparently not affected. Thus, should able modulate, depending subclass selected environment, production length biologically active/inactive fragments.