ATX-F8-117 induces FVIII-specific T-cell unresponsiveness in humanized HLA-DR2tg mice. (A) Groups of 8 to 10 HLA-DR2tg mice (FVIII^+/+) were pretreated with a combination of peptides P1 and P17 (ATX-F8-117), according to the dose-escalation scheme (0.1-1-10-100-100-100µg of each peptide), or PBS. Following pretreatment, mice were immunized with peptides PRCLT and DNIMV in complete Freund adjuvant (CFA) containing 400 µg of heat-killed M tuberculosis. (B) T-cell activation was assessed 10 days after the immunization by determining the proliferation of splenocytes upon restimulation with rhFVIII. Data are mean ± standard error of the mean (SEM). *P < .05, **P < .01, repeated-measures 2-way analysis of variance (ANOVA) of log-transformed data. (C) Cytokine content of the cell culture supernatants restimulated with rhFVIII was analyzed using cytokine bead array technology. Data are mean ± SEM. **P < .01, ***P < .001, ****P < .0001, repeated-measures 2-way ANOVA and Bonferroni post test. IFN-g, interferon-γ; SI, stimulation index.