Human monocyte–derived dendritic cells expressing HLA-DRB1*1501 process and present immunodominant epitopes of human FVIII that were identified in E17 HLA-DRB1*1501 mice. T-cell hybridomas derived from E17 HLA-DRB1*1501 mice (E17 mice with human MHC class II) or from conventional E17 mice (E17 mice with murine MHC class II) were cocultured with human monocyte-derived dendritic cells, which express HLA-DRB1*1501, in the presence of human FVIII for 24 hours. Culture supernatants were collected and analyzed for the release of IL-2. Presented is the fold induction of IL-2, reflecting the IL-2 levels found in culture supernatants of cultures restimulated with FVIII compared with culture supernatants of cultures restimulated in the absence of FVIII with culture medium only.