Kinetics of C1 activation by a monoclonal anti-C1q antibody and its (Fab)2 fragments.
Monoclonal antibody 1H11, which binds to the "head" portion of C1q, has been shown to be a strong, stoichiometric activator of C1, the first component of human complement, maximal activation being achieved at a ratio of one antibody-combining site per one C1q head; moreover, this activation occurs even in the presence of C1-inhibitor, as reported previously. In the present paper, the kinetics of activation are shown to be biphasic; that is, a portion of the C1 is activated very rapidly, and the remainder slowly. These two processes can be separated by the order of mixing of preincubated components; thus, only the rapid activation rate is observed if C1q and the monoclonal antibody are preincubated together and are added subsequently to a mixture of C1r2C1S2 and C1-inhibitor. Only the slow activation rate is observed when C1q, C1r2C1S2, and C1-inhibitor are preincubated and are added subsequently to monoclonal antibody 1H11. Similar results are obtained by using either the intact 1H11 antibody or else the (Fab)2 obtained from it by proteolytic digestion and purification. The rapid phase is independent of the concentration of 1H11 over the range employed; the slow phase depends on 1H11 concentration. Plausible activation schemes are presented to explain the two distinct activation rate processes, and kinetic models are developed which provide a reasonable simulation of the experimental data.
D000911:Antibodies, Monoclonal / Q000276:immunology*; D003166:Complement Activating Enzymes / Q000276:immunology*; D003167:Complement Activation; D003172:Complement C1 / Q000276:immunology* / Q000378:metabolism*; D015922:Complement C1q; D004306:Dose-Response Relationship, Immunologic; D006207:Half-Life; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007700:Kinetics
D000911:Antibodies, Monoclonal; D003172:Complement C1; D007140:Immunoglobulin Fab Fragments; D015922:Complement C1q; D003166:Complement Activating Enzymes