Proteome-based epitopic peptide scanning along PSA

The specific definition of the immunogenic peptide repertoire from tumor-associated-antigens (TAAs) is of crucial importance for designing effective immunotherapeutical treatments. Multiple mechanisms, at different levels and in complementary manners, contribute to the generation of immunogenic peptides. Using as an experimental model the prostate specific antigen (PSA) and a murine monoclonal antibody (MAb) raised against human PSA, the role of PSA peptide 1) similarity to the murine proteome, 2) affinity to H2-Ad/Ed molecules, and 3) proteasomal cleavage pattern were investigated. We report that the core of the interaction between the anti-PSA MAb ER-PR8 and the prostatic antigen is located in the pentapeptide motif PSA27–31GGWEC. The pentapeptide motif is characterized by having no sequence similarity to the murine proteome and a low number of potential proteolytic sites.