Mechanism of action of blocking immunoglobulin G for Neisseria gonorrhoeae.

Abstract

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 PIl 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 PIl 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.

Antibodies to Keyhole Limpet Hemocyanin Cross-React with an Epitope on the Polysaccharide Capsule of Cryptococcus neoformans and Other Carbohydrates: Implications for Vaccine Development

“…In addition, KLH cross-reacts with nonprotective S. mansoni epitopes, and not the protective ones (10). Just as GXM contains protective and nonprotective epitopes, similar findings have been reported with other carbohydrate Ags (14,15). There is a possibility that other, yet unknown, nonprotective epitopes that cross-react with KLH exist on carbohydrates of other organisms, possibly resulting in deleterious effects.…”

“…In the case of C. neoformans, these epitopes have been defined based on their reactivity with mAbs that do or do not prolong the life of mice lethally infected with C. neoformans (12,13). In addition, there is evidence that Abs directed against nonprotective epitopes of the polysaccharide capsule of Schistosoma mansoni, N. meningitidis, and C. neoformans can block the efficacy of protective Abs and even enhance infection (11)(12)(13)(14)(15).…”

Human natural anti-Gal IgG regulates alternative complement pathway activation on bacterial surfaces.

“…We studied 90 blood isolates from patients with Gram-negative sepsis who were hospitalized at the Beth Israel (BI) Hospital in Boston, Massachusetts and the Veterans Administration Medical Center (SF VAMC) in San Francisco, California, and 27 Gram-negative facultatively aerobic bacteria isolated from the stools of healthy volunteers from our laboratory in San Francisco. 44 isolates were collected consecutively from blood cultures submitted from July, 1987 through June, 1988 to the SF VAMC Clinical Laboratory and represented all such isolates of which we are aware. An additional blood isolate from the VAMC, S. marcescens #7, has been extensively characterized (12).…”

Towards a New Challenge in TB Control: Development of Antibody-Based Protection

“…Immune serum is a polyclonal preparation that includes antibodies to multiple specificities and isotypes; consequently, polyclonal sera may contain blocking antibodies [33] and antibodies of different functional categories that can affect the outcome of infection. For example, IgG3 murine monoclonal antibodies protects against Streptococcus pneumoniae and M. tuberculosis but fails to protect against C. neoformans [34].…”