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/K^b^‐transgenic mice expressing chimeric human (α1 and α2 domains of HLA‐A2402) and mouse (α3, transmembrane and cytoplasmic domains of H‐2K^b^) class I molecules. Immunization of these HLA‐A2402/K^b^‐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, PSA~152–160~, encoded by human prostate‐specific antigen. Staining with HLA tetramers showed that the cytotoxic activity induced by immunizing with PSA~152–160~ in HLA‐A2402/K^b^ transgenic mice was HLA‐A2402‐restricted and CD8‐dependent. Therefore, PSA~152–160~ might be a candidate peptide for vaccination of HLA‐A24^+^ patients with prostate cancer. Our results suggest that HLA‐A2402/K^b^ 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. © 2002 Wiley‐Liss, Inc.