title: H chain C domains influence the strength of binding of IgG for streptococcal group A carbohydrate.
abstract: We have produced a panel of murine anti-streptococcal mAbs, expressing identical V domains and different H chain C domains, corresponding to the IgG3, IgG1, and IgG2b subclasses. We have used these mAb to evaluate the role of IgG subclass-specific C region determinants in modulating the interaction between antibody and the bacterial surface. We report, for the first time, that V region-identical murine IgG of different subclasses exhibit substantial differences in binding to specific Ag; IgG3 mAb binds more strongly to streptococci than the IgG1 and IgG2b mAb or IgG3-derived F(ab')2 fragments. Furthermore, the IgG3 mAB binds cooperatively to the bacteria, whereas the IgG1, IgG2b, and IgG3-derived F(ab')2 fragments do not exhibit significant cooperativity, which suggests that differences in Fc region structure can affect antibody binding to multivalent Ag by modulating the potential for cooperative binding. These results suggest a plausible mechanism by which murine IgG3 could be more effective, than other antibodies bearing identical V domains, but of different gamma-subclass, in mediating bacterial immunity.
authors.affiliation: Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: L J
authors.initials: LJ
authors.lastname: Cooper
authors.forename: J C
authors.initials: JC
authors.lastname: Schimenti
authors.forename: D D
authors.initials: DD
authors.lastname: Glass
authors.forename: N S
authors.initials: NS
authors.lastname: Greenspan
mesh_terms: D000818:Animals; D000937:Antigen-Antibody Reactions; D001666:Binding Sites, Antibody / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007127:Immunoglobulin Constant Regions / Q000502:physiology*; D007074:Immunoglobulin G / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000502:physiology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013291:Streptococcus / Q000276:immunology*
chemical_list: D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D011135:Polysaccharides, Bacterial; C044260:streptococcal group A cell wall carbohydrate