First Author | Gotoh M | Year | 2002 |
Journal | Int J Cancer | Volume | 100 |
Issue | 5 | Pages | 565-70 |
PubMed ID | 12124806 | Mgi Jnum | J:131893 |
Mgi Id | MGI:3774791 | Doi | 10.1002/ijc.10509 |
Citation | Gotoh M, et al. (2002) Development of HLA-A2402/K(b) transgenic mice. Int J Cancer 100(5):565-70 |
abstractText | 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 (alpha1 and alpha2 domains of HLA-A2402) and mouse (alpha3, 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. |