Mechanism of action of blocking immunoglobulin G for Neisseria gonorrhoeae.
Blocking immunoglobulin G (IgG) inhibits complement-mediated killing of serum-resistant Neisseria gonorrhoeae (GC) in immune human serum. We examined the mechanism of action of blocking IgG. Presensitization of GC with increasing concentrations of blocking IgG or F(ab')2 before incubation with bactericidal antibody and absorbed pooled normal human serum increased consumption and deposition of the third component of human complement (C3) and the ninth component of human complement (C9) but inhibited killing in dose-related fashion. We next showed that blocking IgG or F(ab')2 partially inhibited binding of bactericidal IgG to GC. Also, binding of a monoclonal antibody recognizing GC outer membrane protein PIII was almost completely inhibited by blocking F(ab')2, confirming other work (Rice, P. A., M. R. Tam, and M. S. Blake, manuscript submitted for publication) showing that PIII is a target for blocking antibody. Studies of the C3 deposition site showed that one quarter of the C3 deposited on GC in the presence of blocking IgG bound covalently to the antibody molecule. Finally, 125I-GC constituents with covalently bound C3 were affinity purified on Sepharose bearing antibodies to C3 and identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis. C3 deposition on a 40,000-mol wt surface protein was enhanced six- to ninefold by blocking IgG, which indicates that the site of complement deposition was altered by blocking antibody. These studies show that blocking IgG competes with bactericidal antibody for binding to GC, but enhances rather than blocks complement activation, and leads to complement deposition at new sites that do not result in serum killing.
D000907:Antibodies, Bacterial / Q000276:immunology*; D000936:Antigen-Antibody Complex; D001665:Binding Sites; D001667:Binding, Competitive; D003167:Complement Activation; D003176:Complement C3 / Q000276:immunology*; D003186:Complement C9 / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D009344:Neisseria gonorrhoeae / Q000276:immunology*
D000907:Antibodies, Bacterial; D000936:Antigen-Antibody Complex; D003176:Complement C3; D003186:Complement C9; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G