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Analysis of GPIIb/IIIa receptor number by quantification of 7E3 binding to
human platelets
CL Wagner, MA Mascelli, DS Neblock, HF Weisman, BS Coller and RE Jordan
Centocor, Research and Development, Malvern, PA, USA.
A large number of glycoprotein (GP) IIb/IIIa receptors are present on the
surface of platelets. Studies to define precisely the number of GPIIb/IIIa
receptors using specific monoclonal antibodies (MoAbs) or fibrinogen
binding have, however, yielded varying estimates of receptor number. To
refine the quantitative estimation of GPIIb/IIIa receptors on resting
platelets, we have used the MoAb 7E3, which has high affinity for
GPIIb/IIIa. Quantitative binding studies were performed using radiolabeled
conjugates of 7E3 IgG, as well as fragments and derivatives of 7E3. For
platelets obtained from any single individual, the numbers of 7E3 F(ab')2
and IgG molecules bound per platelet were equivalent (approximately
40,000), whereas the number of Fab molecules bound per platelet was
consistently approximately twofold higher (approximately 80,000). To
investigate the basis of the quantitative disparity in binding of intact
7E3 and 7E3 F(ab')2 versus 7E3 Fab, we studied the binding of a newly
constructed, bispecific (Fab')2 molecule containing only a single 7E3
combining site. Because this construct bound to the same extent as the Fab
species, the larger size of the intact 7E3 and 7E3 F(ab')2 molecules could
not explain the reduced number of molecules that bound per platelet
compared to the Fab fragment. Rather, it appears that the valency of the
antibody is the critical factor determining the number of antibody
molecules bound per platelet. Thus, we conclude that the binding of 7E3 Fab
corresponds most closely with surface GPIIb/IIIa number and that the number
of GPIIb/IIIa receptors is approximately 80,000 per platelet.
Volume 88,
Issue 3,
pp. 907-914,
08/01/1996
Copyright © 1996 by The American Society of Hematology
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