C1 inhibitor removes the entire C1qr2s2 complex from anti-C1Q monoclonal antibodies with low binding affinities.
Evidence is presented for a new C1 Inhibitor (C1 INH) function. C1 INH was capable of dislodging the entire C1qr2s2 complex from C1-activating substances that bound weakly to the globular heads of C1q. Two different mouse IgG1 monoclonal antibodies with different affinities for C1q globular heads were compared for their complement-activating properties in the presence of normal human serum. As expected the higher affinity monoclonal antibody (Qu) was more effective in binding C1q and causing C1-mediated C4b deposition. Unexpectedly, time responses of C1 (C1q) binding to immobilized 3C7 reached a peak then gradually decreased. However, C1q remained constantly bound to immobilized Qu. These results indicated that after C1 activation in human serum, the entire C1 complex (including C1q) was dislodged from 3C7, but not from immobilized Qu. The addition of purified C1 INH to purified C1, which had bound to immobilized 3C7, resulted in removal of C1 (C1q). Removal of the entire C1qr2s2 did not occur when C1 INH preparations were first neutralized by the addition of purified activated C1s. In summary, it is suggested that C1 INH plays a prominent role in dislodging the entire C1qr2s2 from immunoglobulin preparations which have a low binding affinity for the globular heads of C1q.
Chen
C H
CH
Department of Microbiology and Immunology, Division of Oral Biology of the Department of Stomatology, College of Dental Medicine, Medical University of South Carolina, Charleston, SC, USA.
Lam
C F
CF
Boackle
R J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D015153:Blotting, Western; D003167:Complement Activation; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D015922:Complement C1q / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice
D000911:Antibodies, Monoclonal; D003174:Complement C1 Inactivator Proteins; D015922:Complement C1q