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Thromb Haemost 1994; 72(06): 964-972
DOI: 10.1055/s-0038-1648991
Original Article
Schattauer GmbH Stuttgart

Partial Inhibition of Platelet Aggregation and Fibrinogen Binding by a Murine Monoclonal Antibody to GPIIIa: Requirement for Antibody Bivalency

Jeffery L Kutok
The Division of Hematology, State University of New York at Stony Brook, Stony Brook, NY, USA
,
Barry S Coller
The Division of Hematology, State University of New York at Stony Brook, Stony Brook, NY, USA
› Author Affiliations
Further Information

Publication History

Received 01 August 1994

Accepted 24 August 1994

Publication Date:
06 July 2018 (online)

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Summary

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

 

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