ArticleJournal of biomedical science2022
Identification of human MHC-I HPV18 E6/E7-specific CD8 + T cell epitopes and generation of an HPV18 E6/E7-expressing adenosquamous carcinoma in HLA-A2 transgenic mice.
Article in Journal of biomedical science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 7 citations in OpenAlex.
- Conserved Influenza Epitopes Delivered via MHC-I-Functionalized Nanocarriers Induce Influenza-Specific CTL Responses.Immune network · 2026Article
- Genetic Variation of HPV53 and the Identification of T-Cell Epitopes.Microorganisms · 2026Article
- Integrated in silico-in vitro identification of high-affinity TCR-Like antibodies targeting HPV18 E6/E7 for cervical cancer detection.Archives of virology · 2026Article
- A mouse model of HPV-associated cervicovaginal carcinosarcoma with comparative analysis to human clinical cases.Cell & bioscience · 2026Article
- CD8+ T-cell Antitumor Immunity via Human iNKT-DC Conjugates.Cancer immunology research · 2026Article
- Optimized Multi-Epitope Norovirus Vaccines Induce Robust Humoral and Cellular Responses in Mice.Vaccines · 2025Article
- Article
- Development of an innovative approach for early diagnosis of cervical cancer using TCR‑like antibodies targeting HPV18 E6 and E7 peptides.Molecular medicine reports · 2025Article
- Viral vector-based therapeutic HPV vaccines.Clinical and experimental medicine · 2024Review
- Viral Vector-BasedVaccines · 2024Article
- The role of CD4MedComm · 2023Review
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6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHuman Papillomavirus type 18 (HPV18) is a high-risk HPV that is commonly associated with cervical cancer. HPV18 oncogenes E6 and E7 are associated with the malignant transformation of cells, thus the identification of human leukocyte antigen (HLA)-restricted E6/E7 peptide-specific CD8 + T cell epitopes and the creation of a HPV18 E6/E7 expressing cervicovaginal tumor in HLA-A2 transgenic mice will be significant for vaccine development.
methodsIn the below study, we characterized various human HLA class I-restricted HPV18 E6 and E7-specific CD8 + T cells mediated immune responses in HLA class I transgenic mice using DNA vaccines encoding HPV18E6 and HPV18E7. We then confirmed HLA-restricted E6/E7 specific CD8 + T cell epitopes using splenocytes from vaccinated mice stimulated with HPV18E6/E7 peptides. Furthermore, we used oncogenic DNA plasmids encoding HPV18E7E6(delD70), luciferase, cMyc, and AKT to create a spontaneous cervicovaginal carcinoma model in HLA-A2 transgenic mice.
resultsTherapeutic HPV18 E7 DNA vaccination did not elicit any significant CD8 + T cell response in HLA-A1, HLA-24, HLA-B7, HLA-B44 transgenic or wild type C57BL/6 mice, but it did generate a strong HLA-A2 and HLA-A11 restricted HPV18E7-specific CD8 + T cell immune response. We found that a single deletion of aspartic acid (D) at location 70 in HPV18E6 DNA abolishes the presentation of HPV18 E6 peptide (aa67-75) by murine MHC class I. We found that the DNA vaccine with this mutant HPV18 E6 generated E6-specific CD8 + T cells in HLA-A2. HLA-A11, HLA-A24 and HLA-b40 transgenic mice. Of note, HLA-A2 restricted, HPV18 E7 peptide (aa7-15)- and HPV18 E6 peptide (aa97-105)-specific epitopes are endogenously processed by HPV18 positive Hela-AAD (HLA-A
conclusionsWe characterized various human HLA class I-restricted HPV18 E6/E7 peptide specific CD8 + T cell epitopes in human HLA class I transgenic mice. We demonstrated that HPV18 positive Hela cells expressing chimeric HLA-A2 (AAD) do present both HLA-A2-restricted HPV18 E7 (aa7-15)- and HPV18 E6 (aa97-105)-specific CD8 + T cell epitopes. A mutant HPV18E6 that had a single deletion at location 70 obliterates the E6 presentation by murine MHC class I and remains oncogenic. The identification of these human MHC restricted HPV antigen specific epitopes as well as the HPV18E6/E7 expressing adenosquamous cell carcinoma model may have significant future translational potential.
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