PLATELET ACTIVATION-INDUCED BY A MURINE MONOCLONAL-ANTIBODY DIRECTED AGAINST A NOVEL TETRA-SPAN ANTIGEN

MAb 14A2.H1 identifies a novel low-abundance platelet surface antigen, PETA-3, which is a member of the tetra-span (TM4) family. This MAb br ings about platelet aggregation and mediator release, which is complet ely inhibitable by prostaglandin E(1), and partially inhibitable by as pirin and ketanserin. Platelet activation by MAb 14A2.H1 is dependent on interaction with both the platelet Fc receptor, Fc gamma RII, and t he specific antigen as it was prevented by either a blocking MAb to Fc gamma RII (IV.3) or F(ab')(2) fragments of 14A2.H1. The extent of pla telet activation by the antibody varied considerably between donors, a nd is believed to reflect the polymorphism of Fc gamma RII. Subaggrega ting concentrations of 14A2.H1 synergized with other platelet agonists , ADP, adrenaline, collagen and serotonin, indicating signalling via a pathway distinct from these activators. Synergy was also blocked by M Ab IV.3, or F(ab')(2) fragments of 14A2.H1. The similar low copy numbe r of PETA-3 and Fc gamma RII in the platelet membrane (approximately 1 000/platelet), together with the dependence on Fc gamma RII for activa tion by MAb 14A2.H1, suggests that PETA-3 may be a component of the Fc gamma RII signal transducing complex in platelets.