| Anti-tumor immunity is mainly mediated by cellular immune responses with cytotoxic T lymphocytes (CTL) as the major effector cells. Unlike recognition of intact antigens by antibodies, CTL recognizes antigenic peptides presented on the surface of cells in the context of MHC class I molecules. Antigenic peptides are produced from degradation of proteins in cytosol. The degraded short peptides (8 to 12 amino acids in length) are selectively transported by transporter associated with antigen processing (TAP) into endoplasmic reticulum wherein the peptides bind to the newly-synthesized MHC class I molecules to form antigenic peptide-MHC class I molecule complex. The complex is then transported via Golgi exocytosis pathway to the cell surface to be recognized by the T-cell receptor (TCR) of CD8~+ T cells. According to this knowledge of antigen processing and presentation, any proteins of tumor cells different in quality and/or quantity from normal cells can serve as candidate tumor antigens. Tumor suppressor gene p53 is the most commonly mutated gene in human cancers. Mutant p53 protein which has a longer half-life and accumulates abnormally in tumor cells would be a possible target of host immune attack.Synthetic peptide vaccination is a novel strategy for cancer immuno-therapy. Different alleles of MHC class I molecules demonstrate different peptide binding requirements, i.e., specific peptide sequences known as MHC class I allele-specific consensus motifs or peptide binding motifs are required. Based on the peptide binding motifs, peptides capable of binding to a given MHC class I molecule may be predicted from the amino acid sequence of a tumor antigen.Prediction of antigenic peptides is a sine qua non for the design and development of peptide-based vaccines. In this study, we attempt to predict CTL epitopes (antigenic peptides) of mouse mutant p53 proteins and to explore the possibility of inducing specific CTL responses with synthetic... |
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