Cytophilic activity of enzymatically derived fragments of guinea pig IgG2.

The hydrolysis products from short term exposure of guinea pig IgG2 to papain and pepsin have been characterized. Papain hydrolysis liberates 4 types of Fc fragment, only one of which retains both an interchain disulfide bond and an intact CH2 domain, cFc, mol.wt. 56 000. The other three fragments noncovalently linked Fc (nFc) (mol.wt. 56 000), incomplete Fc (iFc) (mol.wt. 39 000) and Fc' (23 000) represent further degradation products of covalently linked complete Fc (cFc). The cytophilic activities of these fragments as well as F(ab')2 and pFc' from pepsin hydrolysis, were studied to determine the domain(s) responsible for binding to homologous peritoneal macrophages. Only the native immunoglobulin and the intact cFc manifested cytophilic activity; in particular pepsin-derived pFc' and Fc' were inactive. Following mild reduction and alkylation, performed to affect only the interchain disulfide bonds, the cytophilic activity of cFc was markedly reduced. The low cytophilic activity in the pFc' fragment suggests that the CH2 domains play a major part in binding to the macrophage Fc receptor through a site(s) stabilized by the interchain disulfide bonds.