Human p53(264-272) HLA-A2 binding peptide is an immunodominant epitope in DNA-immunized HLA-A2 transgenic mice.
C57BL/10 mice transgenic for HLA-A2 were immunized with either a full-length DNA-construct of the tumor suppressor p53 or with a minigene encoding the p53-derived immunodominant peptide p53(264)LLGRNSFEV272 (L9V). Vaccination with the full-length p53 construct induced potent cytotoxic activity of splenocytes against L9V-pulsed target cells after in vivo re-stimulation. Vaccination with the L9V-encoding minigene likewise induced specific anti-L9V cytotoxicity in vitro. Subsequent experiments revealed that peptide-pulsed dendritic cells were the most efficient cell types for in vitro re-stimulation. In concordance with this, immunization with L9V-pulsed dendritic cells also induced a potent and specific anti-L9V cytotoxic response in vitro. These data show that HLA-A2/peptide-specific cytotoxic immunity can be generated in vivo against the same immunodominant epitope by immunizing either with full-length DNA or with a DNA minigene encoding the immunodominant peptide epitope.
Petersen
T R
TR
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Denmark.
Bregenholta
S
S
Pedersen
L O
LO
Nissen
M H
MH
Claesson
M H
MH
D000818:Animals; D019556:COS Cells; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D016056:Immunodominant Epitopes; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology*
D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53; D019444:Vaccines, DNA