Identification and Characterization of the Immunodominant Rat HER-2/neu MHC Class I Epitope Presented by Spontaneous Mammary Tumors from HER-2/neu-Transgenic Mice

• Published in: The Journal of immunology (1950) Vol. 170; no. 8; pp. 4273 - 4280
• Main Authors: Ercolini, Anne M, Machiels, Jean-Pascal H, Chen, Yi Cheng, Slansky, Jill E, Giedlen, Martin, Reilly, R. Todd, Jaffee, Elizabeth M
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.04.2003
• Subjects: 3T3 Cells; Adoptive Transfer; Animals; Antigen Presentation - genetics; Cell Line, Transformed; Clone Cells; Epitopes, T-Lymphocyte - administration & dosage; Epitopes, T-Lymphocyte - biosynthesis; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Genes, erbB-2 - immunology; Graft Rejection - genetics; Graft Rejection - immunology; Growth Inhibitors - administration & dosage; Growth Inhibitors - biosynthesis; Growth Inhibitors - genetics; Growth Inhibitors - immunology; H-2 Antigens - genetics; H-2 Antigens - immunology; H-2 Antigens - isolation & purification; H-2 Antigens - metabolism; Histocompatibility Antigen H-2D; Humans; Immunodominant Epitopes - genetics; Immunodominant Epitopes - isolation & purification; Immunodominant Epitopes - metabolism; Injections, Intravenous; Mammary Neoplasms, Experimental - genetics; Mammary Neoplasms, Experimental - immunology; Mammary Neoplasms, Experimental - pathology; Mammary Neoplasms, Experimental - prevention & control; Mice; Mice, Inbred Strains; Mice, Transgenic; Peptide Fragments - administration & dosage; Peptide Fragments - biosynthesis; Peptide Fragments - genetics; Peptide Fragments - immunology; Peptide Mapping; Rats; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - transplantation; Vaccines, DNA - administration & dosage; Vaccines, DNA - genetics; Vaccines, DNA - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.170.8.4273

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.