Tumor Immunity by Hydrophobic Appendage Bearing Antigens

摘要

Amplification of the stimulatory ability of the tumor Ag requires modifications in the tumor Ag. Previous approaches used replacement of the amino acids in the CTL, epitope sequence. Only a few of the resulting CTL showed better recognition of the tumor Ag than the CTL induced by the wild-type epitope. To address this question, we developed a novel approach focused on changes in the side chains of the epitopes. This required first identification of the side chains pointing toward the T-cell receptor. We addressed this question by developing molecular modeling of the peptide HLA-A2 complex. A first point of analysis was Ser 5. We found that removal of the hydroxyl group enhanced the immunogenicity of the tumor Ag (J. Immunol.,. in press). A second point of analysis was the Ala7.