A Conserved E7-derived Cytotoxic T Lymphocyte Epitope Expressed on Human Papillomavirus 16-transformed HLA-A2+ Epithelial Cancers
العنوان: | A Conserved E7-derived Cytotoxic T Lymphocyte Epitope Expressed on Human Papillomavirus 16-transformed HLA-A2+ Epithelial Cancers |
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المؤلفون: | Karen S. Anderson, Guang Lan Zhang, Angelika B. Riemer, Ellis L. Reinherz, Bruce B. Reinhold, Derin B. Keskin, Maris Handley, Vladimir Brusic |
بيانات النشر: | American Society for Biochemistry and Molecular Biology, 2010. |
سنة النشر: | 2010 |
مصطلحات موضوعية: | T cell, Papillomavirus E7 Proteins, Immunology, Epitopes, T-Lymphocyte, Human leukocyte antigen, CD8-Positive T-Lymphocytes, Biochemistry, Epitope, Mass Spectrometry, Interferon-gamma, Transduction, Genetic, Cell Line, Tumor, MHC class I, HLA-A2 Antigen, medicine, Cytotoxic T cell, Humans, Immunoprecipitation, Molecular Biology, Human papillomavirus 16, biology, HLA-A Antigens, ELISPOT, Computational Biology, Cell Biology, Oncogene Proteins, Viral, Virology, Repressor Proteins, CTL, medicine.anatomical_structure, biology.protein, Peptides, T-Lymphocytes, Cytotoxic |
الوصف: | Human Papillomavirus 16 (HPV-16) has been identified as the causative agent of 50% of cervical cancers and many other HPV-associated tumors. The transforming potential/tumor maintenance capacity of this high risk HPV is mediated by two viral oncoproteins, E6 and E7, making them attractive targets for therapeutic vaccines. Of 21 E6 and E7 peptides computed to bind HLA-A*0201, 10 were confirmed through TAP-deficient T2 cell HLA stabilization assay. Those scoring positive were investigated to ascertain which were naturally processed and presented by surface HLA molecules for CTL recognition. Because IFNγ ELISpot frequencies from healthy HPV-exposed blood donors against HLA-A*0201-binding peptides were unable to identify specificities for tumor targeting, their physical presence among peptides eluted from HPV-16-transformed epithelial tumor HLA-A*0201 immunoprecipitates was analyzed by MS(3) Poisson detection mass spectrometry. Only one epitope (E7(11-19)) highly conserved among HPV-16 strains was detected. This 9-mer serves to direct cytolysis by T cell lines, whereas a related 10-mer (E7(11-20)), previously used as a vaccine candidate, was neither detected by MS(3) on HPV-transformed tumor cells nor effectively recognized by 9-mer specific CTL. These data underscore the importance of precisely defining CTL epitopes on tumor cells and offer a paradigm for T cell-based vaccine design. |
اللغة: | English |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::746eb502ef7ecb7d21e4c1b38d60ed1e https://europepmc.org/articles/PMC2937992/ |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....746eb502ef7ecb7d21e4c1b38d60ed1e |
قاعدة البيانات: | OpenAIRE |
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