Mapping factor VIII inhibitor epitopes using hybrid human/porcine factor VIII molecules

Four epitopes in the factor VIII (FVIII) molecule have been identified that constitute the targets for antibodies in most inhibitor plasmas. These epitopes are located in the A2, A3 and C2 domains and in the activation peptide (ar3 region) of the FVIII light chain. We have developed a method for mapping FVIII epitopes using recombinant hybrid human/porcine FVIII molecules. Ongoing studies continue to provide higher resolution maps of these epitopes. The manipulation of inhibitor epitopes using recombinant DNA technology may lead to improved forms of FVIII that have lower antigenicity and/or lower immunogenicity.