Abstract
The HER-2/neu (neu-N)-transgenic mice are a clinically relevant model of breast cancer. They are derived from the parental FVB/N mouse strain and are transgenic for the rat form of the proto-oncogene HER-2/neu (neu). In this study, we report the identification of a MHC class I peptide in the neu protein that is recognized by CD8(+) T cells derived from vaccinated FVB/N mice. This 10-mer was recognized by all tumor-specific FVB/N T cells generated regardless of the TCR Vbeta region expressed by the T cell or the method of vaccination used, establishing it as the immunodominant MHC class I epitope in neu. T cells specific for this epitope were able to cure FVB/N mice of transplanted neu-expressing tumor cells, demonstrating that this is a naturally processed peptide. Altered peptide analogs of the epitope were analyzed for immunogenicity. Vaccination with dendritic cells pulsed with a heteroclitic peptide provided FVB/N and neu-N mice with increased protection against tumor challenge as compared with mice immunized with dendritic cells loaded with either wild-type or irrelevant peptide. Discovery of this epitope allows for better characterization of the CD8(+) T cell responses in the neu-N mouse model in which neu-specific tolerance must be overcome to produce effective antitumor immunity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Adoptive Transfer
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Animals
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Antigen Presentation* / genetics
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Cell Line, Transformed
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Clone Cells
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Epitopes, T-Lymphocyte / administration & dosage
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Epitopes, T-Lymphocyte / biosynthesis
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / immunology
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Genes, erbB-2 / immunology*
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Graft Rejection / genetics
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Graft Rejection / immunology
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Growth Inhibitors / administration & dosage
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Growth Inhibitors / biosynthesis
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Growth Inhibitors / genetics
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Growth Inhibitors / immunology
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H-2 Antigens / genetics
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H-2 Antigens / immunology
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H-2 Antigens / isolation & purification
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H-2 Antigens / metabolism*
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Histocompatibility Antigen H-2D
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Humans
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Immunodominant Epitopes / genetics
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Immunodominant Epitopes / isolation & purification*
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Immunodominant Epitopes / metabolism*
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Injections, Intravenous
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Mammary Neoplasms, Experimental / genetics
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Mammary Neoplasms, Experimental / immunology*
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Mammary Neoplasms, Experimental / pathology
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Mammary Neoplasms, Experimental / prevention & control
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Mice
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Mice, Inbred Strains
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Mice, Transgenic
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Peptide Fragments / administration & dosage
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Peptide Fragments / biosynthesis
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Peptide Fragments / genetics
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Peptide Fragments / immunology
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Peptide Mapping
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Proto-Oncogene Mas
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Rats
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / transplantation
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Vaccines, DNA / administration & dosage
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Vaccines, DNA / genetics
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Vaccines, DNA / immunology
Substances
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Epitopes, T-Lymphocyte
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Growth Inhibitors
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H-2 Antigens
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Histocompatibility Antigen H-2D
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Immunodominant Epitopes
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MAS1 protein, human
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Peptide Fragments
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Proto-Oncogene Mas
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Vaccines, DNA