Interaction of Neisseria gonorrhoeae with classical complement components, C1-inhibitor, and a monoclonal antibody directed against the Neisserial H.8 antigen.
Strains of Neisseria gonorrhoeae were used to evaluate bactericidal and opsonic properties of McAb 10 directed against the Neisserial outer membrane antigen, H.8. Gonococci were either serum resistant in the absence but serum sensitive in the presence, of McAb 10, or serum sensitive or serum resistant regardless of the presence of McAb 10. Strain JS3, which fell in the former category, was used in subsequent studies. C1 zymogen formed by reassociation of isolated C1 subunits was not directly activated by JS3 in the presence or absence of C1-inhibitor. JS3 thus was unable to directly activate the classical pathway independently of antibody. When purified classical pathway components were used to deposit C3 on JS3 in the absence of serum regulatory proteins or antibodies, added C1-inhibitor reduced C3 binding to background levels. When McAb 10 was present, C3 binding was unaffected by C1-inhibitor. Covalently bound, large molecular weight C3 alpha-chain-gonococcal complexes were disbanded by methylamine release of ester linkages. Released 125I-C3 migrated as C3b without degradation by gonococcal proteases. Purified classical components alone or McAb 10 alone facilitated JS3 killing by neutrophils; when combined, the two provided maximal killing. Levels of McAb 10 that only slightly increase C3 deposition on JS3 are bactericidal in serum and maximally opsonic in combination with purified classical pathway components.
Schweinle
J E
JE
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Hitchcock
P J
PJ
Tenner
A J
AJ
Hammer
C H
CH
Frank
M M
MM
Joiner
K A
KA
D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001770:Blood Bactericidal Activity; D003172:Complement C1 / Q000276:immunology; D003174:Complement C1 Inactivator Proteins / Q000276:immunology*; D003171:Complement Pathway, Classical; D006801:Humans; D008970:Molecular Weight; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis
D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins; D003172:Complement C1; D003174:Complement C1 Inactivator Proteins; C055700:H.8 protein (Neisseria)