Identification of the murine H-2Db and human HLA-A*0201 MHC class I-restricted HPV6 E7-specific cytotoxic T lymphocyte epitopes

Shiwen Peng, Austin Mattox, Simon R. Best, Anca M. Barbu, James A. Burns, Belinda Akpeng, Jessica Jeang, Benjamin Yang, Eiichi Ishida, Chien Fu Hung, Tzyy Choou Wu, Sara I. Pai

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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-2Db-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-2Db-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.

Original languageEnglish
Pages (from-to)261-271
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume65
Issue number3
DOIs
Publication statusPublished - 2016 Mar 1

Keywords

  • Human papillomavirus
  • Immunotherapy
  • MHC class I
  • Recurrent respiratory papillomatosis
  • T cell epitope
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Identification of the murine H-2D<sup>b</sup> and human HLA-A*0201 MHC class I-restricted HPV6 E7-specific cytotoxic T lymphocyte epitopes'. Together they form a unique fingerprint.

  • Cite this

    Peng, S., Mattox, A., Best, S. R., Barbu, A. M., Burns, J. A., Akpeng, B., Jeang, J., Yang, B., Ishida, E., Hung, C. F., Wu, T. C., & Pai, S. I. (2016). Identification of the murine H-2Db and human HLA-A*0201 MHC class I-restricted HPV6 E7-specific cytotoxic T lymphocyte epitopes. Cancer Immunology, Immunotherapy, 65(3), 261-271. https://doi.org/10.1007/s00262-016-1793-x