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

被引：79

作者：

Ercolini, AM ^{[1
]}

Machiels, JPH ^{[1
]}

Chen, YC ^{[1
]}

Slansky, JE ^{[1
]}

Giedlen, M ^{[1
]}

Reilly, RT ^{[1
]}

Jaffee, EM ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Ctr, Dept Oncol,Grad Program Immunol, Baltimore, MD 21231 USA

来源：

JOURNAL OF IMMUNOLOGY | 2003年 / 170卷 / 08期

关键词：

D O I：

10.4049/jimmunol.170.8.4273

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 inummogenicity. 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.

引用

页码：4273 / 4280

页数：8

共 73 条

[1] The immigration dilemma: Avoiding the tragedy of the commons - Hardin,G [J].