Requirements for the opsonic activity of human IgG directed to type 6 group A streptococci: net basic charge and intact Fc region.
By two independent techniques for separating human opsonic IgG for group A type 6 streptococci into fast- and slow-migrating fractions, it was found that the opsonic activity was localized within the basic charge population. This charge dependence was found to be a characteristic of the IgG isolated from three individuals. When the fast- and slow-migrating IgG fractions were tested for their ability to bind to purified M6 protein, antibodies in both opsonic and nonopsonic populations exhibited binding activity, with the majority being located within the opsonic IgG in two of the three individuals; the third displayed greater binding in the nonopsonic population. The functional difference observed in the antibody populations to this M antigen may be a reflection of the net charge within the area of the antibody binding site, which suggests that the opsonic antibodies need to bind to acidic residues along the outer surface of the fibrillar M protein molecule. F(ab')2 fragments prepared from both human and rabbit type 6 opsonic IgG were still able to bind to the M6 molecule but were unable to mediate opsonization of type 6 streptococci. However, the F(ab')2 fragments had the capacity to enhance or amplify the opsonic activity of low concentrations of opsonic IgG molecules. The results suggest that the M protein molecule may function as an active inhibitor of phagocytosis and that F(ab')2 fragments from opsonic IgG have the capacity to neutralize the "active" determinants on the molecule, thus allowing lower concentrations of IgG with functional Fc receptors to mediate phagocytosis.
D001666:Binding Sites, Antibody; D001770:Blood Bactericidal Activity; D004588:Electrophoresis, Cellulose Acetate; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G / Q000378:metabolism*; D007525:Isoelectric Focusing; D009895:Opsonin Proteins / Q000032:analysis / Q000276:immunology*; D010587:Phagocytosis; D011961:Receptors, Fc; D013297:Streptococcus pyogenes / Q000378:metabolism*
D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D011961:Receptors, Fc