Within my research-group Cellular Hemostasis at Sanquin in Amsterdam we aim to integrate biochemical research on blood coagulation factors with both molecular and cellular immunological approaches. Over the last years we have focused on the interaction of FVIII with antigen presenting cells. My group identified a exposed loop in the C1 domain that is crucially involved in binding to antigen presenting cells. In follow-experiments we showed that modification of this loop reduces the immunogenicity of FVIII in murine hemophilia A. In collaborative study with Dr. Kate Pratt we have clarified a mechanism that explains the onset of inhibitor development in a subset of patients with mild hemophilia A. We have also established a novel and innovative peptide presentation assay that has allowed for the identification of FVIII and ADAMTS13 derived peptides that are presented on MHC class II. In my presentation I will discuss how this newly developed assay can be used to assess the potential imunogenicity of existing and novel biotherapeutics.