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DOI: 10.1055/s-0037-1615962
Fine Mapping of Inhibitory Anti-factor V Antibodies Using Factor V C2 Domain Mutants
Identification of Two Antigenic Epitopes Involved in Phospholipid BindingPublication History
Received
28 August 2000
Accepted after revision
11 January 2001
Publication Date:
12 December 2017 (online)
Summary
Hemorrhagic factor V inhibitors frequently bind to the second C-type (C2) domain of factor V and interfere with phospholipid binding. To define specific residues recognized by inhibitors from four patients (one bovine thrombin-induced and three spontaneous antibodies), epitope mapping was performed using recombinant human factor V lacking most of the B-type domain (FV des B) and alanine-substituted mutants within the C2 domain (FV des B C2 mutants). FV des B C2 mutants located in the region between Lys2060 and Glu2069 were resistant to inhibition by three IgG preparations including the bovine thrombin-induced antibody in both prothrombinase and phospholipid-binding assays. In contrast, mutations at Lys2087 and Lys2092/ Glu2096 were significantly resistant to inhibition by the fourth IgG preparation in both prothrombinase and phospholipid-binding assays. These results confirm interference of phospholipid binding by hemorrhagic factor V inhibitors and support the role(s) of these residues in phospholipid binding.
Presented in part at the 41st Annual Meeting of the American Society of Hematology, New Orleans, Louisiana, December 3–7, 1999
* Department of Clinical Laboratory Science, College of Health Sciences, Korea University, Korea;
† Instituto de Biologia Molecular de Barcelona, CSIC, Spain