The Fc valency of an immune complex is the decisive factor for binding to low-affinity Fc gamma receptors.

Tetanus toxoid (TT) was complexed with two human monoclonal antibodies. The antibodies recognized different, nonrepeating epitopes. The complexes formed were characterized by gel filtration and isokinetic sucrose density gradient centrifugation. It was found that in antigenic excess the separate antibodies formed a complex of one antibody molecule and two TT molecules [IgG1-(TT)2 and IgG3-(TT)2]. In cases where equal amounts of TT and both antibodies were mixed, a dimeric complex [IgG1-(TT)2-IgG3] was formed. The binding of these immune complexes to human neutrophils and eosinophils was studied. Whereas the immune complexes containing one antibody did not bind to either cell type, the two-antibody complex bound to both. This indicates that not the sterical change in the Fc part of an antibody molecule after binding an antigen, but the Fc valency of an immune complex is the decisive factor in Fc receptor interaction with neutrophilic and eosinophilic granulocytes.