C1 inhibitor removes the entire C1qr(2)s(2) complex from anti-C1Q monoclonal antibodies with low binding affinities

Evidence is presented for a new CI Inhibitor (C1 INH) function. C1 INH was capable of dislodging the entire C1qr(2)s(2) complex from Cl-activating sub stances that bound weakly to the globular heads of Clq. Two different mouse IgG1 monoclonal antibodies with different affinities for Clq globular head s 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 Clq and causing C1-mediated C4b depositi on. Unexpectedly, time responses of CI (Clq) binding to immobilized 3C7 rea ched a peak then gradually decreased. However, Clq remained constantly boun d to immobilized Qu. These results indicated that after C1 activation in hu man serum, the entire C1 complex (including Clq) was dislodged from 3C7, bu t not from immobilized Qu. The addition of purified C1 INH to purified C1, which had bound to immobilized 3C7, resulted in removal of C1 (Clq). Remova l of the entire C1qr(2)s(2) did not occur when CI INH preparations were fir st neutralized by the addition of purified activated Cls. In summary, it is suggested that C1 INH plays a prominent role in dislodging the entire C1qr (2)s(2) from immunoglobulin preparations which have a low binding affinity for the globular heads of Clq.