التفاصيل البيبلوغرافية
| العنوان: |
Identification of the murine H-2D and human HLA-A*0201 MHC class I-restricted HPV6 E7-specific cytotoxic T lymphocyte epitopes. |
| المؤلفون: |
Peng, Shiwen1, Mattox, Austin2, Best, Simon3, Barbu, Anca4, Burns, James4, Akpeng, Belinda4, Jeang, Jessica1, Yang, Benjamin1, Ishida, Eiichi4, Hung, Chien-Fu, Wu, Tzyy-Choou, Pai, Sara4 sara.pai@mgh.harvard.edu |
| المصدر: |
Cancer Immunology, Immunotherapy. Mar2016, Vol. 65 Issue 3, p261-271. 11p. |
| مصطلحات موضوعية: |
*MAJOR histocompatibility complex, *CYTOTOXIC T cells, *EPITOPES, *PAPILLOMAVIRUS diseases, *IMMUNE response, *CALRETICULIN |
| مستخلص: |
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-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-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. [ABSTRACT FROM AUTHOR] |
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