Monoclonal Antibodies to Ligand-occupied Conformers of Integrin aIIbP 3 ( Glycoprotein IIb-IIIa ) Alter Receptor Affinity , Specificity , and Function *

Occupancy of integrin receptors induces conformational changes in the receptor, resulting in exposure of novel interactive sites termed ligand-induced binding sites (LIBS). We report here that Fab fragments of certain antibodies against LIBS on integrin ( ~ I I b a 3 (platelet glycoprotein IIb-IIIa) block platelet aggregation. Thus, certain LIBS or the regions surrounding them may participate in events required for platelet aggregation. In addition, certain anti-aIIbB3 LIBS Fab fragments stimulated platelet aggregation. This was due to induction of fg binding to aII&, apparently by shifting a conformational equilibrium between a “resting” and an “activated” state of al&. Some of the activating anti-LIBS Fab fragments also induced high affinity fibronectin binding to aII&, whereas others did not. Thus, changes in the conformation of this integrin modulate both the specificity and affinity of ligand recognition.