Factor VIII epitopes recognized with inhibitory monoclonal antibodies.
To test whether anti-idiotypic immunoregulation of factor VIII(FVIII)-inhibiting antibodies could be feasible in hemophiliacs, we assayed the minimal number and range of immunogenic, functional FVIII epitopes to which a series of murine anti-FVIII monoclonal antibodies (MAb) were directed. Rabbit anti-idiotypic sera to 7 MAb were prepared and used in competitive immunoradiometric assays to test Id similarities among 36 murine MAb. At least 12 immunogenic and functional epitopes were found on the FVIII molecule. The large range of target loci for FVIII inhibitors will make their immunoregulation by anti-idiotypic methods difficult.
Tiarks
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Department of Medicine, University of Massachusetts Medical Center, Worcester.
Humphreys
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Pechet
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D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000032:analysis / Q000276:immunology*; D005169:Factor VIII / Q000037:antagonists & inhibitors / Q000276:immunology*; D006467:Hemophilia A / Q000276:immunology; D006801:Humans; D015592:Immunoradiometric Assay / Q000295:instrumentation / Q000379:methods; D051379:Mice; D011817:Rabbits; D013997:Time Factors
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000939:Epitopes; D005169:Factor VIII