PARTIAL INHIBITION OF PLATELET-AGGREGATION AND FIBRINOGEN BINDING BY A MURINE MONOCLONAL-ANTIBODY TO GPIIIA - REQUIREMENT FOR ANTIBODY BIVALENCY

We produced a murine monoclonal antibody. 7H2, and localized its epito pe to one or more small regions on platelet glycoprotein (GP) IIIa. 7H 2-IgG and 7H2-F(ab')(2) completely inhibit platelet aggregation and fi brinogen binding at low agonist concentrations, but only partially inh ibit aggregation and fibrinogen binding at high agonist concentrations ; 7H2-Fab has no effect on aggregation or fibrinogen binding at any ag onist concentration. 7H2-IgG binds to the entire platelet population a s judged by flow cytometry. At near saturating concentrations, similar to 40,000 7H2-IgG antibody molecules bind per platelet. In contrast, similar to 80,000 7H2 Fab molecules bind per platelet, suggesting that 7H2-IgG binding is bivalent. 7H2 was unable to inhibit fibrinogen bin ding to purified, immobilized GPIIb/IIIa. These data indicate that the bivalent binding of 7H2 to GPIIIa is required for its partial inhibit ion of fibrinogen binding to platelets, perhaps through dimerization o f GPIIb/lIIa surface receptors (or more complex GPIIb/IIIa redistribut ion triggered by 7H2 binding) resulting in limited accessibility of fi brinogen to its binding site(s).