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Abstract

The invention provides a method for the improved processing efficiency of T cell tumor antigen epitopes using bioinformatic means. The proteolytic sites in the generation of 47 experimentally identified HLA-A2.1-restricted immunodominant tumor antigen epitopes was compared to those of 52 documented HLA-A2.1-restricted immunodominant viral antigen epitopes. The amino acid frequencies in the C-terminal cleavage sites of the tumor antigen epitopes, as well as several positions within the 10 amino acid (aa) flanking regions, were significantly different from those of the viral antigen epitopes. These two groups of epitopes may be cleaved by distinct sets of proteasomes and peptidases or similar enzymes with lower efficiencies for tumor epitopes, targeted activation of the immunoproteasomes and peptidases can be achieved that mediate the cleavage of viral epitopes in order to more effectively generate tumor antigen epitopes thus enhancing antigen-specific tumor immunotherapy.

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