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

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

› Author Affiliations

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

References
1 Meyer D, Girma JP. von Willebrand Factor: structure and function. Thromb Haemost 1993; 70: 99-104
2 Sadler JE. von Willebrand factor. J Biol Chem 1991; 266: 22777-80
3 Bonthron D, Orr EC, Mitsock LM, Ginsburg D, Handin RI, Orkin SH. Nucleotide sequence of pre-pro-von Willebrand factor cDNA. Nucleic Acids Res 1986; 14: 7125-7
4 Girma JP, Kalafatis M, Pietu G, Lavergne JM, Chopek MW, Edgington TS, Meyer D. Mapping of distinct von Willebrand factor domains interacting with platelet GPIb and GPIIb/IIIa and with collagen using monoclonal antibodies. Blood 1986; 67: 1356-66
5 Foster PA, Fulcher CA, Marti T, Titani K, Zimmerman TS. A major Factor VIII binding domain resides within the amino-terminal 272 amino acid residues of von Willebrand factor. J Biol Chem 1987; 262: 8443-6
6 Takahashi Y, Kalafatis M, Girma JP, Sewerin K, Andersson LO, Meyer D. Localization of a factor VIII binding domain on a 34 kilodalton fragment of the N-terminal portion of von Willebrand factor. Blood 1987; 70: 1679-82
7 Fujimura Y, Titani K, Holland LZ, Russell SR, Roberts JR, Elder JH, Ruggeri ZM, Zimmerman TS. von Willebrand factor. A reduced and alkylated 52/48-kDa fragment beginning at amino acid residue 449 contains the domain interacting with platelet glycoprotein lb. J Biol Chem 1986; 261: 381-5
8 Mohri H, Fujimura Y, Shima M, Yoshioka A, Houghten RA, Ruggeri ZM, Zimmerman TS. Structure of the von Willebrand factor domain interacting with glycoprotein lb. J Biol Chem 1988; 263: 17901-4
9 Berndt MC, Ward CM, Booth WJ, Castaldi PA, Mazurov AV, Andrews RK. Identification of aspartic acid 514 through glutamic acid 542 as a glycoprotein Ib-IX complex receptor recognition sequence in von Willebrand factor. Mechanism of modulation of von Willebrand factor by ristocetin and botrocetin. Biochemistry 1992; 31: 11144-51
10 Roth GJ, Titani K, Hoyer LW, Hickey MK. Localization of binding sites within human von Willebrand factor for monomeric type III collagen. Biochemistry 1986; 25: 8357-61
11 Fretto LJ, Fowler WE, McCaslin DR, Erickson HP, McKee PA. Substructure of human von Willebrand factor: proteolysis by V8 and characterization of two functional domains. J Biol Chem 1986; 261: 15679-89
12 Sobel M, Soler DF, Kermode JC, Harris RK. Localization and characterization of a heparin binding domain peptide of human von Willebrand factor. J Biol Chem 1992; 267: 8857-62
13 Christophe O, Obert B, Meyer D, Girma JP. The binding domain of von Willebrand factor to sulfatides is distinct from those interacting with glycoprotein-Ib, heparin, and collagen and resides between amino acid residues Leu 512 and Lys 673. Blood 1991; 78: 2310-7
14 Berndt MC, Booth WJ, Andrews RK, Castaldi PK. Definition of von Willebrand factor (vWF)-GP IB-IX complex interaction using vWF-based peptides. Thromb Haemost 1991; 65: 748 (abstr)
15 Denis C, Baruch D, Kielty CM, Ajzenberg N, Christophe O, Meyer D. Localization of von Willebrand Factor binding domains to endothelial extracellular matrix and to type VI collagen. Arteriosclerosis and Thrombosis 1993; 13: 398-406
16 Plow EF, Srouji AJ, Meyer D, Margucric G, Ginsberg MK. Evidence that three adhesive proteins interact with a common recognition site on activat ed platelets. J Biol Chem 1984; 259: 5388-91
17 Pietu G, Ribba AS, Cherel G, Meyer D. Epitope mapping by cDNA expression of a monoclonal antibody which inhibits the binding of von Willebrand Factor to platelet glycoprotein Ilb/IIIa. Biochem J 1992; 284: 711-5
18 Bahou WF, Ginsburg D, Sikkink R, Litwiller R, Fass DK. A monoclonal antibody to von Willebrand factor (vWF) inhibits factor VIII binding. Localization of its antigenic determinant to a nonadecapeptide at the amino terminus of the mature vWF polypeptide. J Clin Invest 1989; 84: 56-61
19 Ginsburg D, Bockenstedt PL, Allen EA, Fox DA, Foster PA, Ruggeri ZM, Zimmerman TS, Montgomery RR, Bahou WF, Johnson TA, Yang AY. Fine mapping of monoclonal antibody epitopes on human von Willebrand factor using a recombinant peptide library. Thromb Haemost 1992; 67: 166-71
20 Young RA, Bloom BR, Groskinsky CM, Ivanyi JT, Thomas D, Davis RK. Dissection of mycobacterium tuberculosis antigens using recombinant DNA. Proc Natl Acad Sci 1985; 82: 2583-7
21 Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N. Enzymatic amplification of (3-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 1985; 230: 1350-4
22 Pietu G, Ribba AS, de Paillette L, Cherel G, Lavergne JM, Bahnak BR, Meyer D. Molecular study of von Willebrand disease: Identification of potential mutations in patients with type IIA and IIB. Blood Coag Fibrinol 1992; 3: 415-21
23 Meyer D, Zimmerman TS, Obert B, Edgington TK. Hybridoma antibodies to human von Willebrand factor. I. Characterization of seven clones. Br J Haematol 1984; 57: 597-608
24 Pietu G, Ribba AS, Meulien P, Meyer D. Localization within the 106 N-terminal amino acids of von Willebrand factor (vWF) of the epitope corresponding to a monoclonal antibody which inhibits vWF binding to factor VIII. Biochem Biophys Res Comm 1989; 163: 618-26
25 Gaucher C, Jorieux S, Mercier B, Oufkir D, Mazurier C. The Normandy variant of von Willebrand disease. Characterization of a point mutation in the von Willebrand factor gene. Blood 1991; 77: 1937-41
26 Girma JP, Takahashi Y, Yoshioka A, Diaz J, Meyer D. Ristocetin and botrocetin involve two distinct domains of von Willebrand factor for binding to platelet membrane glycoprotein lb. Thromb Haemost 1990; 64: 326-32
27 Pietu G, Fressinaud E, Girma JP, Nieuwenhuis K, Rothschild C, Meyer D. Binding of von Willebrand factor to collagen and to collagen-stimulated platelets. J Lab Clin Med 1987; 109: 637-46
28 Nokes TJC, Mahmoud NA, Savidge GF, Goodall AH, Meyer D, Edgington TS, Hardisty RM. von Willebrand factor has more than one binding site for platelets. Thromb Res 1984; 34: 361-6
29 Steinbuch M, Audran R. The isolation of IgG from mammalian sera with the aid of caprylic acid. Arch Biochem Biophys 1969; 134: 279-84
30 Ware J, Toomey JR, Stafford DK. Localization of a factor VUI-inhibiting antibody epitope to a region between residues 338 and 362 of factor VIII heavy chain. Proc Natl Acad Sci USA 1988; 85: 3165-9
31 Ware J, Toomey JR, Stafford DW. Epitope localization of anti-factor VIII monoclonal antibodies determined by recombinant peptides. Thomb Haemost 1989; 61: 225-9
32 Mcgraw R, Frazier D, de Serres M, Reisner H, Stafford D. Antigenic determinant in human coagulation factor IX: immunological screening and DNA sequence analysis of recombinant phage map a monoclonal antibody to residues 111 through 132 of the zymogen. Blood 1986; 67: 1344-8
33 Frazier D, Smith KJ, Cheung WF, Ware J, Lin SW, Thompson AR, Reisner H, Bajaj SP, Stafford DW. Mapping of monoclonal antibodies to human factor IX. Blood 1989; 74: 971-7
34 Nunberg JH, Rodgers G, Gilbert JH, Snead RK. Method to map antigenic determinants recognized by monoclonal antibodies: localization of a determinant of virus neutralization on the feline leukemia virus envelope protein gp70. Proc Natl Acad Sci USA 1984; 81: 3675-9
35 Mehra V, Sweetser D, Young RK. Efficient mapping of protein antigenic determinants. Proc Natl Acad Sci USA 1986; 83: 7013-7
36 Lamb JR, Ivanyi J, Rees ADM, Rothbard JB, Howland K, Young RA, Young DK. Mapping of T cell epitopes using recombinant antigens and synthetic peptides. EMBO J 1987; 6: 1245-9
37 Nishino M, Girma JP, Rothschild C, Fressinaud E, Meyer D. A new variant of von Willebrand disease with defective binding to factor VIII. Blood 1989; 74: 1591-9
38 Mazurier C, Dieval J, Jorieux S, Delobel J, Goudemand M. A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF. Characterization of abnormal vWF/FVIII interaction. Blood 1990; 75: 20-6
39 Mazurier C. von Willebrand disease masquerading as haemophilia A. Thromb Haemost 1992; 67: 391-6
40 Kroner PA, Friedman KD, Fahs SA, Scott P, Montgomery RR. Abnormal binding of factor VIII is linked with the substitution of glutamine for arginine 91 in von Willebrand factor in a variant form of von Willebrand disease. J Biol Chem 1991; 266: 19146-9
41 Jorieux S, Tuley EA, Gaucher C, Mazurier C, Sadler JE. The mutation Arg (53) Trp causes von Willebrand disease Normandy by abolishing binding to factor VIII. Studies with recombinant von Willebrand factor. Blood 1992; 79: 563-7
42 Tuley EA, Gaucher C, Jorieux S, Worrall NK, Sadler JE, Mazurier C. Expression of von Willebrand factor Normandy: an autosomal mutation that mimics hemophilia A. Proc Natl Acad Sci USA 1991; 88: 6377-81
43 Ginsburg D, Sadler JE. von Willebrand disease: a database of point mutations insertions and deletions. Thromb Haemost 1993; 69: 177-84
44 Mancuso DJ, Montgomery RR, Adam P. The identification of a candidate mutation in the von Willebrand Factor gene of patients with a variant form of type I von Willebrand disease. Blood 1991 78. (suppl) 67 a (abstr)