表位
CTL公司*
免疫原性
生物
CD8型
启动(农业)
细胞毒性T细胞
人类白细胞抗原
转基因
分子生物学
转基因小鼠
T细胞
抗原
免疫系统
免疫学
体外
基因
遗传学
植物
发芽
作者
Joseph Lustgarten,Matthias Theobald,Colleen Labadie,Drake LaFace,Per A. Peterson,Mary L. Disis,Martin A. Cheever,Linda A. Sherman
标识
DOI:10.1016/s0198-8859(96)00292-3
摘要
The Her-2/neu protooncogene is associated with malignant transformation and aggressive disease. Because of its overexpression in tumor cells and because it has been shown to be immunogenic, this protein represents an excellent target for T-cell immunotherapy. By identifying potential HLA-A2.1-binding peptides from the Her-2/neu sequence, peptides were selected as candidate T-cell epitopes. The immunogenicity of each peptide was evaluated by priming double transgenic mice expressing both the human (hu) CD8 and HLA-A2.1 molecules with synthetic peptides corresponding to these sequences. Because of the lack of interaction between murine CD8 and HLA-A2.1, expression of huCD8 on murine cells facilitates recognition of HLA molecules on human tumor cell lines. This led to the identification of two peptides that elicit an A2-restricted CTL response, one of which has not been previously identified. Both peptidespecific CTL populations were able to specifically lyse A2.1 and Her-2/neu expressing human tumor cells originating from a variety of tissues, demonstrating the utility of this murine model in identifying peptides presented by human cells. However, several Her-2/neu peptides previously reported to be immunogenic for human CTL were found not to be immunogenic in transgenic mice. The basis for these discrepancies is discussed.
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