Premium
Development of HLA‐A2402/K b transgenic mice
Author(s) -
Gotoh Masashi,
Takasu Hideo,
Harada Kenji,
Yamaoka Takashi
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10509
Subject(s) - ctl* , epitope , cytotoxic t cell , human leukocyte antigen , biology , antigen , transgene , peptide vaccine , genetically modified mouse , cd8 , virology , immunology , microbiology and biotechnology , cancer research , genetics , gene , in vitro
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.