Evidence for the Domain Hypothesis: Location of the Site of Cytophilic Activity toward Guinea Pig Macrophages in the CH3 Homology Region of Human Immunoglobulin G

Abstract

Abstract Most of the effector functions of human immunoglobulin G (IgG), such as complement fixation, transplacental transfer, cytophilic activity toward macrophages and control of catabolic rate are mediated through the Fc region of the molecule. Some of these functions have been shown more recently to be associated with particular subfragments of the Fc region corresponding to either the CH2 or CH3 homology regions of the IgG1 heavy chain. Minta and Painter (1) showed that the pFc' fragment which comprises the CH3 homology region was able to interfere with the passive cutaneous anaphylactic reaction in guinea pigs, presumably by competing with antibody for sites on the cutaneous mast cells. Kehoe and Fougereau (2) showed that fragments from the CH2 region of a mouse immunoglobulin were able to activate the complement system when suitably aggregated. More recently Ellerson et al. (3) showed that a fragment comprising the whole CH2 homology region of human IgG was able to activate the complement system when aggregated on polystyrene latex.