This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Murakami, M. Articles by Steller, M. A. Search for Related Content PubMed PubMed Citation Articles by Murakami, M. Articles by Steller, M. A.

Induction of Specific CD8+ T-Lymphocyte Responses Using a Human Papillomavirus-16 E6/E7 Fusion Protein and Autologous Dendritic Cells

Section of Gynecologic Oncology, Surgery Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 20892 [M. M., K. J. G., F. M. M., M. A. S.], and CSL Limited, Parkville, Victoria 3052, Australia [J. A.]

When intracellular viral proteins are degraded, only a limited number of peptide epitopes are capable of eliciting specific CD8⁺ cellular immune responses for a given human leukocyte antigen (HLA) haplotype. We sought to induce CD8⁺ T-lymphocyte (CTL) responses to human papillomavirus-16 (HPV-16) E6 and E7 proteins using a recombinant E6/E7 fusion protein and autologous human dendritic cells (DCs). CTLs were generated by in vitro stimulation using a recombinant HPV-16 E6/E7 fusion protein and autologous DCs from a healthy HLA-A*0201 donor. CTL specificity was assessed by cytokine release assays when the cells were reacted with autologous DC targets coincubated with the E6/E7 fusion protein. These CTLs were also reacted with the immunodominant E7 peptides (E7_11–20 and E7_86–93) and DCs as a target. As a negative control, DCs were incubated with or without an irrelevant control protein (Helicobacter pylori) as target for the E6/E7-induced CTLs. The E6/E7- induced CTLs were capable of specific recognition of target DCs coincubated with E6/E7 but not the control protein. When E6/E7-specific CTLs were reacted with DCs and either E7_11–20 or E7_86–93, specific peptide recognition was also detected. These data demonstrate that specific CTLs can be elicited using autologous human DCs and a HPV-16 E6/E7 fusion protein. Therefore, extracellular viral proteins seem to be engulfed and processed by DCs; then the immunodominant HLA-A2-restricted peptides become available for CD8⁺ T-lymphocyte recognition. These data suggest that vaccine strategies using recombinant viral proteins may overcome the limitation of peptide epitopes for specific HLA haplotypes and may, therefore, permit more generalized clinical application.

This article has been cited by other articles:

				K. Devaraj, M. L. Gillison, and T.-C. Wu DEVELOPMENT OF HPV VACCINES FOR HPV-ASSOCIATED HEAD AND NECK SQUAMOUS CELL CARCINOMA Crit. Rev. Oral. Biol. Med., September 1, 2003; 14(5): 345 - 362. [Abstract] [Full Text] [PDF]

				M. A. Steller Cervical Cancer Vaccines: Progress and Prospects Reproductive Sciences, September 1, 2002; 9(5): 254 - 264. [Abstract] [PDF]

				M. Evans, L. K. Borysiewicz, A. S. Evans, M. Rowe, M. Jones, U. Gileadi, V. Cerundolo, and S. Man Antigen Processing Defects in Cervical Carcinomas Limit the Presentation of a CTL Epitope from Human Papillomavirus 16 E6 J. Immunol., November 1, 2001; 167(9): 5420 - 5428. [Abstract] [Full Text] [PDF]

				M. P. Rudolf, S. C. Fausch, D. M. Da Silva, and W. M. Kast Human Dendritic Cells Are Activated by Chimeric Human Papillomavirus Type-16 Virus-Like Particles and Induce Epitope-Specific Human T Cell Responses In Vitro J. Immunol., May 15, 2001; 166(10): 5917 - 5924. [Abstract] [Full Text] [PDF]

				H. Höhn, H. Pilch, S. Günzel, C. Neukirch, K. Freitag, A. Necker, and M. J. Maeurer Human Papillomavirus Type 33 E7 Peptides Presented by HLA-DR*0402 to Tumor-Infiltrating T Cells in Cervical Cancer J. Virol., July 15, 2000; 74(14): 6632 - 6636. [Abstract] [Full Text]