Cytotoxic T cell epitopes are the targets for a T cell mediated immunotherapy of cancer. The thesis reports on their identification in the tumor associated proteins BCR-ABL and PRAME by the reverse... Show moreCytotoxic T cell epitopes are the targets for a T cell mediated immunotherapy of cancer. The thesis reports on their identification in the tumor associated proteins BCR-ABL and PRAME by the reverse immunology (prediction) strategy. An extended strategy is used, including the analysis of the C-terminal generation of potential epitopes by the proteasome. Novel HLA class I peptide binding assays were developed to enable further epitope discovery. Fundamental studies were performed to identify novel non-proteasomal cytosolic endopeptidases in the HLA class I antigen processing pathway. Nardilysin and thimet oligopeptidase were identified to generate in a concerted action an HLA-A3 restricted CTL epitope from PRAME. The general roles of nardilysin and TOP in class I processing were investigated. Show less
