Cleavage of the Four Human IgG Subclasses with Cathepsin G

Abstract

Cathepsin G, the chymotrypsin-like serine proteinase from human polymorphonuclear leucocytes, cleaves human IgG. The relative susceptibilities of the 4 IgG subclasses to the action of this enzyme were studied kinetically and showed the following decreasing order of susceptibility: IgG3 .mchgt. IgG4 > IgG1 > IgG2. IgG1 and IgG2 produced primarily F(ab'')2 and traces of Fc-related fragments. IgG4 gave rise to both Fab and F(ab'')2 as major products, and small amounts of an Fc-related fragment were detected. The cleavage of IgG3 produced various fragments, depending on the experimental conditions: the primary fragments were Fab and Fch (Fc covalently joined to the extended hinge-region polypeptide of IgG3) and an intermediate Fab-Fch species. Both Fab and Fch were further degraded by cathepsin G. Fch was gradually split, giving rise to 3 subfragments that were finally degraded to dialysable peptides. The enzyme further cleaved the Fab fragment in the heavy-chain portion and released a polypeptide probably representing the VH [heavy chain variable region] domain.