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Journal of Virology, July 2000, p. 6632-6636, Vol. 74, No. 14
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Human Papillomavirus Type 33 E7 Peptides Presented by HLA-DR*0402 to Tumor-Infiltrating T Cells in Cervical Cancer

Hanni Höhn,1 Henryk Pilch,2 Susanne Günzel,2 Claudia Neukirch,1 Kirsten Freitag,1 Antje Necker,3 and Markus J. Maeurer1,*

Department of Medical Microbiology1 and Department of Gynecology,2 Johannes Gutenberg University, Mainz, Germany, and Antibody Department, Beckman/Coulter, Marseille, France3

Received 1 February 2000/Accepted 25 April 2000

Several characteristics make human papillomavirus (HPV) amenable to vaccination. Anti-HPV-directed vaccines are based on the observation that HPV E6 and E7 oncoproteins are constitutively expressed in HPV-positive cervical cancer and may serve as tumor rejection antigens. Five HPV types (16, 18, 31, 33, and 45) account for 80% of cervical cancer. Until now, the type of immune response capable of mediating an effective antitumor response has not been defined. In order to define the anticancer-directed immune response in situ, we characterized CD4+ and CD8+ sorted T cells from peripheral blood lymphocytes, freshly harvested tumor tissue, and tumor-infiltrating lymphocytes (TIL) from a patient with cervical cancer. The HLA-DR-restricted CD4+ T-cell receptor VB16-, VA10-, VA21-, and VA22-positive CD4+ T-cell line derived from TIL recognizes autologous HLA-DR*0402+ (HPV33+) cervical cancer cells, as determined by gamma interferon secretion. Testing of different peptides spanning the E7 gene revealed that the HPV3373-87 peptide ASDLRTIQQLLMGTV represents the immunodominant epitope which can also be presented by the DR*0401 allele to TIL. Such major histocompatibility complex class II-presented peptides represent attractive candidates to augment T-cell responses directed against autologous tumor cells.

* Corresponding author. Mailing address: Hochhaus am Augustusplatz, D-55101 Mainz, Germany. Phone: 49-6131-173645. Fax: 49-6131-175580. E-mail: maeurer{at}mail.uni-mainz.de.

Journal of Virology, July 2000, p. 6632-6636, Vol. 74, No. 14
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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