Development of HLA‐A2402/Kb transgenic mice

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Abstract
HLA-transgenic mice have been developed to facilitate studies of HLA-restricted cytotoxic responses, e.g., for the identification of immunodominant HLA-restricted CTL epitopes and the optimization of peptide or DNA vaccine constructs for human use. We have developed HLA-A2402/Kb-transgenic mice expressing chimeric human (α1 and α2 domains of HLA-A2402) and mouse (α3, transmembrane and cytoplasmic domains of H-2Kb) class I molecules. Immunization of these HLA-A2402/Kb-transgenic mice with various known HLA-A24-restricted immunodominant cancer CTL epitope peptides derived from gp100, MAGE-1, MAGE-3, Her2/neu, CEA and TERT induced HLA-A24-restricted, peptide-specific CTLs. Using these transgenic mice, we identified a novel HLA-A24-restricted CTL epitope, PSA152–160, encoded by human prostate-specific antigen. Staining with HLA tetramers showed that the cytotoxic activity induced by immunizing with PSA152–160 in HLA-A2402/Kb transgenic mice was HLA-A2402-restricted and CD8-dependent. Therefore, PSA152–160 might be a candidate peptide for vaccination of HLA-A24+ patients with prostate cancer. Our results suggest that HLA-A2402/Kb transgenic mice might be useful in the search for HLA-A24-restricted CTL epitopes functioning as human cancer antigens and for the development of peptide-based cancer immunotherapy.