Identification of the murine H-2Db and human HLA-A*0201 MHC class I-restricted HPV6 E7-specific cytotoxic T lymphocyte epitopes
| Autor: | Austin Mattox, Eiichi Ishida, Tzyy Choou Wu, Benjamin Yang, Sara I. Pai, Shiwen Peng, Anca M. Barbu, James A. Burns, Simon R. Best, Jessica Jeang, Belinda Akpeng, Chien Fu Hung |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research T cell Immunology Epitopes T-Lymphocyte Biology Article Epitope DNA vaccination Mice 03 medical and health sciences 0302 clinical medicine Immune system Antigen Cell Line Tumor HLA-A2 Antigen MHC class I Vaccines DNA medicine Animals Humans Immunology and Allergy Cytotoxic T cell Papillomavirus Vaccines Histocompatibility Antigen H-2D Vaccination virus diseases Oncogene Proteins Viral Virology female genital diseases and pregnancy complications Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis biology.protein Female Calreticulin CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | Cancer Immunology, Immunotherapy. 65:261-271 |
| ISSN: | 1432-0851 0340-7004 |
| Popis: | Recurrent respiratory papillomatosis is caused by human papillomavirus (HPV) infection, most commonly types 6 (HPV-6) and 11 (HPV-11). Due to failed host immune responses, HPV is unable to be cleared from the host, resulting in recurrent growth of HPV-related lesions that can obstruct the lumen of the airway within the upper aerodigestive tract. In our murine model, the HPV-6b and HPV-11 E7 antigens are not innately immunogenic. In order to enhance the host immune responses against the HPV E7 antigen, we linked calreticulin (CRT) to HPV-6b E7 and found that vaccinating C57BL/6 mice with the HPV-6b CRT/E7 DNA vaccine is able to induce a CD8+ T cell response that recognizes an H-2D(b)-restricted E7aa21-29 epitope. Additionally, vaccination of HLA-A*0201 transgenic mice with HPV-6b CRT/E7 DNA generated a CD8+ T cell response against the E7aa82-90 epitope that was not observed in the wild-type C57BL/6 mice, indicating this T cell response is restricted to HLA-A*0201. In vivo cytotoxic T cell killing assays demonstrated that the vaccine-induced CD8+ T cells are able to efficiently kill target cells. Interestingly, the H-2D(b)-restricted E7aa21-29 sequence and the HLA-A*0201-restricted E7aa82-90 sequence are conserved between HPV-6b and HPV-11 and may represent shared immunogenic epitopes. The identification of the HPV-6b/HPV-11 CD8+ T cell epitopes facilitates the evaluation of various immunomodulatory strategies in preclinical models. More importantly, the identified HLA-A*0201-restricted T cell epitope may serve as a peptide vaccination strategy, as well as facilitate the monitoring of vaccine-induced HPV-specific immunologic responses in future human clinical trials. |
| Databáze: | OpenAIRE |
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