Fine mapping of monoclonal antibody epitopes on human von Willebrand factor using a recombinant peptide library. Thromb Haemost 1992 Jan 23;67(1):166-71
Date
01/23/1992Pubmed ID
1377414DOI
10.1055/s-0038-1648400Scopus ID
2-s2.0-0026508968 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
A recombinant human von Willebrand factor (vWF) cDNA fragment library was constructed in lambda gt11 for the localization of anti-vWF monoclonal antibody epitopes. Twelve of 21 monoclonal antibodies screened identified epitopes expressed in lambda gt11 as beta-galactosidase fusion proteins. By sequence analysis, these antigenic determinants were localized to segments ranging from 17 to 105 amino acids in length. Four epitopes apparently shared by more than one antibody were identified, suggesting the presence of immuno-dominant epitopes within vWF. Monoclonal antibody C3, which blocks factor VIII (FVIII) binding to vWF, bound to the same epitope previously identified by a second monoclonal antibody which also blocks this function, suggesting that this region may be at or near the vWF/FVIII binding domain. Three antibodies recognize the same region within the vWF A2 repeat. Mutations near this region appear to be responsible for Type IIA von Willebrand's disease. The co-localization of these antibodies suggests that this domain might be exposed on the surface of vWF, consistent with its apparent increased sensitivity to plasma proteases.
Author List
Ginsburg D, Bockenstedt PL, Allen EA, Fox DA, Foster PA, Ruggeri ZM, Zimmerman TS, Montgomery RR, Bahou WF, Johnson TAAuthor
Robert R. Montgomery MD Adjunct Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antibodies, MonoclonalDNA
Epitopes
Gene Library
Humans
Peptide Fragments
Recombinant Fusion Proteins
von Willebrand Factor