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Related Collections Hemostasis, Thrombosis, and Vascular Biology Plenary Papers Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2001, Vol. 98, No. 1, pp. 13-19 PLENARY PAPER Structure of a factor VIII C2 domain-immunoglobulin G4 Fab complex: identification of an inhibitory antibody epitope on the surface of factor VIII Paul Clint Spiegel Jr, Marc Jacquemin, Jean-Marie R. Saint-Remy, Barry L. Stoddard, and Kathleen P. Pratt From the Graduate Program in Biomolecular Structure and Design, University of Washington, and Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; and Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Campus Gasthuisberg, Leuven, Belgium. The development of an immune response to infused factor VIII is a complication affecting many patients with hemophilia A. Inhibitor antibodies bind to antigenic determinants on the factor VIII molecule and block its procoagulant activity. A patient-derived inhibitory immunoglobulin G4 antibody (BO2C11) produced by an immortalized memory B-lymphocyte cell line interferes with the binding of factor VIII to phospholipid surfaces and to von Willebrand factor. The structure of a Fab fragment derived from this antibody complexed with the factor VIII C2 domain was determined at 2.0 Å resolution. The Fab interacts with solvent-exposed basic and hydrophobic side chains that form a membrane-association surface of factor VIII. This atomic resolution structure suggests a variety of amino acid substitutions in the C2 domain of factor VIII that might prevent the binding of anti-C2 inhibitor antibodies without significantly compromising the procoagulant functions of factor VIII. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. L. Meeks, J. F. Healey, E. T. Parker, R. T. Barrow, and P. Lollar Nonclassical anti-C2 domain antibodies are present in patients with factor VIII inhibitors Blood, August 15, 2008; 112(4): 1151 - 1153. [Abstract] [Full Text] [PDF] S. Planque, M. A. Escobar, K. C. Smith, H. Taguchi, Y. Nishiyama, E. Donnachie, K. P. Pratt, and S. Paul Covalent Inactivation of Factor VIII Antibodies from Hemophilia A Patients by an Electrophilic FVIII Analog J. Biol. Chem., May 2, 2008; 283(18): 11876 - 11886. [Abstract] [Full Text] [PDF] A. Vencesla, M. A. 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