IgG molecules exert important effector functions including complement-dependent cytotoxicity (CDC). Different IgG isotypes induce CDC effect with variation, largely due to their differential binding to C1q, the initiating molecule of the classical CDC pathway. Here we report a method to characterize the binding of IgG to C1q using label-free technique. With this method, we determined the binding affinities of multiple IgG1, IgG2 and IgG4 antibodies to C1q. To explore whether antigen binding to antibodies affects C1q binding, we assessed the binding of Trastuzumab and Adalimumab with bound antigen proteins to C1q. The results showed that although the two tested IgG1 mAbs alone bind C1q similarly, their FC binding to C1q was significantly impacted by antigen binding to the Fab. The data suggested that the first step of complement pathway, whether C1q binds target cell bound antibody molecules, may significantly affect the CDC activities of antibody drugs.
[1]Shanghai Chemparmer, Dept Biol, 720 Cailun Rd, Shanghai 201203, Peoples R China;
[2]Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China
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