Abstract: The present invention provides methods for the identification of CD4+ T-cell epitopes in the sequences of various proteins, namely, human cytokines and cytokine receptors, as well as the production of peptides which when incorporated into the protein sequence, are no longer capable of initiating the CD4+ T-cell response. In some embodiments, the present invention provides means and compositions suitable for reducing the immunogenicity of cytokines and cytokines receptors such as interferon-?, soluble tumor necrosis factor receptor-1, erythropoietin, and thrombopoietin.