Antigenic competition and bystander suppression may play roles in mediating the decreased immunogenicity of pdFVIII. Plasma-derived concentrates contain additional protein constituents that compete with FVIII for MHC II presentation. As a result, there is a decreased probability that a given antigen-presenting cell will simultaneously express FVIII-bound MHC class II cells and interact with an FVIII-specific CD4⁺ T cell. Similarly, Tregs against other protein components in pdFVIII may elicit bystander suppression that either inhibits FVIII-specific T cells or polarizes their differentiation into Tregs.