<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Identification of target T cell epitopes for a\r\ntherapeutic HPV16 vaccine"^^ . "To rationally design therapeutic human papillomavirus (HPV) vaccines, it is important to know which\r\nT cell epitopes are present on HPV-transformed cells. HPV affects the cellular antigen processing\r\nmachinery, thus not every epitope derived from viral proteins is necessarily presented by human\r\nleukocyte antigen (HLA) molecules on the cancer cell surface.\r\nHPV16 has been identified as the causative agent in 50% of all cervical cancer cases and in\r\napproximately 95% of all extra-cervical mucosal HPV-induced tumors. The transforming potential of\r\nhigh-risk HPVs is mediated by two consistently expressed viral oncoproteins, E6 and E7. As the\r\ninduction and maintenance of the malignant phenotype depend on these two proteins, they are ideal\r\ntargets for immunotherapy. A therapeutic vaccine that is applicable to everyone without prior HLA\r\ntyping needs to contain epitopes for the major HLA types. To date, HPV T cell epitopes have mostly\r\nbeen determined for the most prevalent HLA type, HLA-A2. We now aim to identify HPV16 E6 and\r\nE7 T cell epitopes for the HLA-A3, HLA-A11 and HLA-A24 supertypes.\r\nDifferent in silico prediction algorithms were used to predict prospective epitopes from the E6 and E7\r\nproteins derived from the HPV16 reference sequence for the mentioned HLA supertypes. In total, 74\r\nepitopes, comprised of 8 to 11mer peptides, were predicted for HLA-A3, 96 epitopes for HLA-A11\r\nand 95 epitopes for HLA-A24. In competition-based cellular binding assays, 22 previously known\r\nbinding peptides were confirmed and 78 novel binding peptides were identified. Additionally, HPV16\r\nvariants harbored in our HPV16-positive cell line collection were determined and peptide binding to\r\nHLA-A24 was shown for seven out of 20 tested HPV16 variant peptides.\r\nEvaluation of prediction server performance based on the generated data suggested different optimal\r\nprediction servers depending on peptide length and on the HLA type. NetMHC and NetMHCcons\r\nwere shown to be the best predictors overall.\r\nImmunogenicity of identified binding peptides was investigated by screening long-term memory\r\nresponses in healthy donors. To this end, peptide-specific short-term T cell lines were generated from\r\nperipheral blood mononuclear cells, which were HLA typed, stimulated with HLA-matching peptides\r\nand cultured for twelve days. Several peptides were identified to be immunogenic. Immunogenicity of\r\nthe four most promising candidate peptides for HLA-A24 could be further confirmed by generation of\r\npeptide-specific long-term T cell lines from healthy HLA-A24-positive donors and subsequent coculture\r\nwith autologous B cells pulsed with the respective peptide. Functional assays, such as IFNγ\r\nELISpot assays and cytotoxicity assays, determined the best vaccine candidates.\r\nIn conclusion, several novel HPV16 E6 and E7 CD8+ T cell epitopes were identified.Verified epitopes\r\nare the basis of rational therapeutic vaccine design and are also important for immunomonitoring\r\npurposes. In addition, they can be employed as a tool for the development of other immunotherapies\r\nsuch as adoptive T cell transfer with transgenic T cell receptors."^^ . "2019" . . . . . . . "Stephanie"^^ . "Hoppe"^^ . "Stephanie Hoppe"^^ . . . . . . "Identification of target T cell epitopes for a\r\ntherapeutic HPV16 vaccine (PDF)"^^ . . . "201506_PhD_thesis_SHoppe.pdf"^^ . . . "Identification of target T cell epitopes for a\r\ntherapeutic HPV16 vaccine (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Identification of target T cell epitopes for a\r\ntherapeutic HPV16 vaccine (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Identification of target T cell epitopes for a\r\ntherapeutic HPV16 vaccine (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Identification of target T cell epitopes for a\r\ntherapeutic HPV16 vaccine (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Identification of target T cell epitopes for a\r\ntherapeutic HPV16 vaccine (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #18938 \n\nIdentification of target T cell epitopes for a \ntherapeutic HPV16 vaccine\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .