Development of HLA-A2402/K(b) transgenic mice

Int J Cancer. 2002 Aug 10;100(5):565-70. doi: 10.1002/ijc.10509.

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 (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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Flow Cytometry
  • H-2 Antigens / genetics*
  • H-2 Antigens / immunology*
  • HLA-A Antigens / genetics*
  • HLA-A Antigens / immunology*
  • Humans
  • Jurkat Cells
  • Mice
  • Mice, Transgenic
  • Models, Animal
  • Molecular Sequence Data
  • Prostate-Specific Antigen / immunology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Substrate Specificity
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection
  • Transgenes / genetics*

Substances

  • H-2 Antigens
  • H-2Kb protein, mouse
  • HLA-A Antigens
  • Recombinant Fusion Proteins
  • Prostate-Specific Antigen