Cancer Immunology, Immunotherapy

, Volume 65, Issue 3, pp 261–271

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

Authors

  • Shiwen Peng
    • Department of PathologyThe Johns Hopkins Medical Institutions
  • Austin Mattox
    • Department of OncologyThe Johns Hopkins Medical Institutions
  • Simon R. Best
    • Department of Otolaryngology-Head and Neck SurgeryThe Johns Hopkins Medical Institutions
  • Anca M. Barbu
    • Department of SurgeryMassachusetts General Hospital
  • James A. Burns
    • Department of SurgeryMassachusetts General Hospital
  • Belinda Akpeng
    • Department of SurgeryMassachusetts General Hospital
  • Jessica Jeang
    • Department of PathologyThe Johns Hopkins Medical Institutions
  • Benjamin Yang
    • Department of PathologyThe Johns Hopkins Medical Institutions
  • Eiichi Ishida
    • Department of SurgeryMassachusetts General Hospital
  • Chien-Fu Hung
    • Department of PathologyThe Johns Hopkins Medical Institutions
    • Department of OncologyThe Johns Hopkins Medical Institutions
  • Tzyy-Choou Wu
    • Department of PathologyThe Johns Hopkins Medical Institutions
    • Department of OncologyThe Johns Hopkins Medical Institutions
    • Department of Obstetrics and GynecologyThe Johns Hopkins Medical Institutions
    • Department of Molecular Microbiology and ImmunologyThe Johns Hopkins Medical Institutions
    • Department of SurgeryMassachusetts General Hospital
Original Article

DOI: 10.1007/s00262-016-1793-x

Cite this article as:
Peng, S., Mattox, A., Best, S.R. et al. Cancer Immunol Immunother (2016) 65: 261. doi:10.1007/s00262-016-1793-x

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.

Keywords

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

Abbreviations

CRT

Calreticulin

HLA

Human leukocyte antigen

HPV

Human papillomavirus

RRP

Recurrent respiratory papillomatosis

Supplementary material

262_2016_1793_MOESM1_ESM.pdf (100 kb)
Supplementary material 1 (PDF 100 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2016