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CD4⁺ Tumor-Infiltrating Lymphocytes in Cervical Cancer Recognize HLA-DR-Restricted Peptides Provided by Human Papillomavirus-E7

Hanni Höhn^*, Henryk Pilch, Susanne Günzel, Claudia Neukirch^*, Christine Hilmes, Andreas Kaufmann^§, Barbara Seliger and Markus J. Maeurer^*

Departments of ^* Medical Microbiology and Gynecology and Third Medical Clinic, Johannes Gutenberg University, Mainz, Germany; and ^§ Department of Gynecology, University of Jena, Jena, Germany

Human papillomavirus (HPV)-encoded proteins may provide targets for CD8⁺ or CD4⁺ T lymphocytes infiltrating into cervical cancer. We established an MHC class II-restricted CD4⁺ T cell line from a patient with cervical cancer that recognizes autologous (HPV35⁺, HPV59⁺) cervical cancer cells and the HLA-DR4-matched cervical cancer cell line Me180 (HPV68⁺) as determined by TNF- secretion. Expression of different HPV-E7 genes in autologous B cells revealed that this T cell line defines a DR4-presented T cell epitope that is shared among the E7 genes of HPV59 and HPV68. MHC class II-presented peptides may be implemented to augment T cell responses directed against autologous tumor cells, particularly if cancer cells lack MHC class I expression, which is a frequent event in the evolution of cervical cancer.

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