Though different CD4+ T cell epitopes from tumor antigens such as CEA [22], p53 [23] or TRP-2 [24] have been defined by in silico prediction, we set out to overcome the drawbacks of this strategy by setting up a comprehensive screening approach based on the immunization of HLA-transgenic mice with recombinant adenovirus encoding human melanoma antigens and subsequent scanning of the T cell responses in vitro with the help of combinatorial antigen-specific peptide libraries. The gene discussed is CD4; the disease is melanoma.