CTL公司*
表位
免疫原性
生物
转基因
转基因小鼠
分子生物学
人类白细胞抗原
体外
病毒学
抗原
主要组织相容性复合体
细胞毒性T细胞
免疫学
CD8型
基因
生物化学
作者
Jeff Alexander,Carla Oseroff,John Sidney,Peggy Wentworth,Elissa Keogh,Gary Hermanson,Francis V. Chisari,Ralph T. Kubo,Howard M. Grey,A Sette
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:1997-11-15
卷期号:159 (10): 4753-4761
被引量:68
标识
DOI:10.4049/jimmunol.159.10.4753
摘要
Transgenic mice expressing chimeric human (alpha1 and alpha2 HLA-A11 domains) and murine (alpha3, transmembrane, and cytoplasmic H-2Kb domains) class I molecules were derived. These mice were used as a model system to study the immunogenicity of human CTL epitopes and also to examine the aspects of Ag processing differences of mice vs man. Immunization of these mice with seven known HLA-A11-restricted CTL epitopes emulsified in IFA resulted in vigorous specific CTL responses. A larger panel of 45 A11-binding peptides was used to examine the relationship between immunogenicity in the HLA-A11/Kb transgenic mice and HLA-A11 binding capacity. Twenty-one of 28 (75%) peptides with high binding affinities (50% inhibitory concentration (IC50), 2-50 nM) and 7 of 13 (54%) intermediate binding peptides (IC50, 50-500 nM range) were immunogenic. In parallel, 19 of these peptides were used for in vitro primary immunizations of PBMC derived from HLA-A11 healthy human donors. It was found that 8 of 8 peptides that were able to elicit CTL in primary human in vitro cultures were also immunogenic in HLA-A11/Kb mice. Finally, HLA-A11/Kb transgenic mice were found to generate an A11/Kb restricted CTL response following immunization with influenza virus A/PR/8/34, suggesting that, at least to some extent, A11 epitopes are generated by transgenic mice as a result of natural in vivo processing and presentation.
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