Epitope Mapping of Inhibitory Monoclonal Antibodies to Human von Willebrand Factor by Using Recombinant cDNA Libraries

Geneviéve Piétu; Anne-Sophie Ribba; Ghislaine Chérel; Virginie Siguret; Bernadette Obert; Christine Rouault; David Ginsburg; Dominique Meyer

doi:10.1055/s-0038-1642524

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1994; 71(06): 788-792
DOI: 10.1055/s-0038-1642524

Review Article

Schattauer GmbH Stuttgart

Epitope Mapping of Inhibitory Monoclonal Antibodies to Human von Willebrand Factor by Using Recombinant cDNA Libraries

Authors

Geneviéve Piétu

INSERM U. 143, Hôpital Bicêtre, Paris, France, University of Michigan, Ann Arbor, MI, USA
Anne-Sophie Ribba

INSERM U. 143, Hôpital Bicêtre, Paris, France, University of Michigan, Ann Arbor, MI, USA
Ghislaine Chérel

INSERM U. 143, Hôpital Bicêtre, Paris, France, University of Michigan, Ann Arbor, MI, USA
Virginie Siguret

INSERM U. 143, Hôpital Bicêtre, Paris, France, University of Michigan, Ann Arbor, MI, USA
Bernadette Obert

INSERM U. 143, Hôpital Bicêtre, Paris, France, University of Michigan, Ann Arbor, MI, USA
Christine Rouault

INSERM U. 143, Hôpital Bicêtre, Paris, France, University of Michigan, Ann Arbor, MI, USA
David Ginsburg

¹Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA
Dominique Meyer

INSERM U. 143, Hôpital Bicêtre, Paris, France, University of Michigan, Ann Arbor, MI, USA

Abstract

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Summary

Two recombinant expression libraries containing small (300-600 base pairs) cDNA fragments of von Willebrand Factor (vWF) were screened in order to map the epitope of monoclonal antibodies (MAbs) to vWF. Among eleven MAbs tested, seven were effectively mapped. The epitopes of MAbs 418 and 522, which inhibit the binding of vWF to Factor VIII (FVIII), were localized between Leu 2 and Arg 53 and between Glu 35 and He 81 of the vWF subunit respectively, within the N-terminal trypsin fragment called SpIII-T4 [amino acids (aa) 1-272] which contains a binding domain for FVIII. The epitope of MAb 710, which inhibits the binding of vWF to glycoprotein lb (GPIb), was identified between Ser 593 and Ser 678 on the tryptic 52/48 kDa fragment (aa 449-728) which contains binding domains for GPIb, collagen, heparin, sulfatides and subendothclium extracellular matrices. The epitope of MAb 723, which does not interfere with any known function of vWF, was localized between Ser 523 and Gly 588. The epitopes of MAb 505 and MAb 400, which inhibit the binding of v WF to collagen, were identified between Leu 927 and Arg 1114 within the SPI fragment (aa 911-1365) corresponding to the central part of the vWF subunit. The epitope of MAb 9, which inhibits the binding of vWF to GPIIb/IIIa, was identified in the C-terminal part of the vWF subunit between Gin 1704 and Asp 1746, the latter being the third aa of the RGD sequence common to adhesive proteins and serving as a recognition site for integrin receptors.

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References

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