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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

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
1   Howard 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
› Author Affiliations
Further Information

Publication History

Received: 10 May 1993

Accepted after resubmission: 02 February 1994

Publication Date:
26 July 2018 (online)

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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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