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

Anne M. Ercolini, Jean Pascal H. Machiels, Yi Cheng Chen, Jill E. Slansky, Martin Giedlen, R. Todd Reilly, Elizabeth M. Jaffee

Research output: Contribution to journalArticle

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 Vβ 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.

Original languageEnglish (US)
Pages (from-to)4273-4280
Number of pages8
JournalJournal of Immunology
Volume170
Issue number8
DOIs
StatePublished - Apr 15 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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