Localization of the binding site for a factor VIII activity neutralizing antibody to amino acid residues Asp1663-Ser1669Article
Shima, M, Fulcher, CA, De Graaf Mahoney, S et al. (1988). Localization of the binding site for a factor VIII activity neutralizing antibody to amino acid residues Asp1663-Ser1669
. JOURNAL OF BIOLOGICAL CHEMISTRY, 263(21), 10198-10203.
Shima, M, Fulcher, CA, De Graaf Mahoney, S et al. (1988). Localization of the binding site for a factor VIII activity neutralizing antibody to amino acid residues Asp1663-Ser1669
. JOURNAL OF BIOLOGICAL CHEMISTRY, 263(21), 10198-10203.
We have identified the Factor VIII amino acid sequence Asp-Tyr-Asp-Asp-Thr-Ile-Ser (1663-1669) as the binding site of a Factor VIII activity neutralizing antibody (28 Bethesda units/mg). The binding site of another neutralizing antibody (10 Bethesda units/mg) overlapped only at Asp1663 and Tyr1664, whereas an antibody with minimal neutralizing activity (0.2 Bethesda units/mg) bound only at Asp1665-Ser1669. Residues comprising antibody binding sites were determined by blocking Factor VIII neutralization and/or binding to insolubilized Factor VIII with overlapping peptides, or with variant peptides in which a single amino acid was deleted or replaced with glycine. Eight additional antibodies to flanking sequences, and with similar affinities for Factor VIII, had little or no neutralizing activity (0-3.0 Bethesda units/mg). These studies suggest that Asp1663 and Tyr1664 may be structural features important to Factor VIII function.
