The Fc gamma receptor on human placental plasma membrane. I. Studies on the binding of homologous and heterologous immunoglobulin G1.

Abstract Plasma membrane vesicles prepared from human placental syncitiotrophoblast have been shown to agglutinate IgG-sensitized red blood cells in an Fc specific manner. This agglutination could be inhibited by monomelic IgG and Fc in a dose-dependent fashion, whereas neither IgA nor IgM were inhibitory. This phenomenon formed the basis of an assay that was used to investigate the binding specificity of the Fc receptor. Experiments with human subclass proteins indicated that IgG1 and 3 (and their corresponding Fc fragments) were more effective inhibitors than IgG2 and 4. The ability of IgG from several species to inhibit agglutination was also determined, and the order observed was human IgG1 > rabbit IgG; mouse IgG2a or guinea pig IgG2 > guinea pig IgG1, mouse IgG1, mouse IgG2b, or dog IgG. IgG from sheep, goat, and cow did not inhibit agglutination over the concentration range tested. A role for the hinge region disulfides in maintaining the binding site on IgG is implied by the fact that both IgG or Fc that has been mildly reduced and alkylated and a mutant IgG1 (DOB) that has a hinge region deletion showed a markedly reduced ability to inhibit agglutination compared to the native molecules. A fragment corresponding to the Cγ3 domain of Fc was not able to inhibit agglutination. This observation supports the suggestion that the site on IgG with which the Fc receptor interacts involves both Cγ2 and Cγ3.