Natural T-HELPER immunity against human papillomavirus type 16 (HPV16) E7-derived peptide epitopes in patients with HPV16-positive cervical lesions: Identification of 3 human leukocyte antigen class II-restricted epitopes

Tumor-specific T-helper (Th) immunity was found to play a pivotal role in t he natural and vaccine-induced immune defense against tumors. Since the maj ority of cervical cancers express human papillomavirus type 16 (HPV16) E7 o ncoprotein, it is important to investigate the Th response against this tar get antigen in detail. By means of PBMC cultures from HLA-typed healthy don ors, we identified the central part of HPV16 E7 (E7(41-72)) as the major im muno-genic region within this antigen. Furthermore, we mapped 3 distinct Th epitopes within this region (DR15/E7(50-62), DR3/E7(43-77) DQ2/E7(35-50)). In a parallel approach, employing IFN-gamma ELISPOT analysis, we detected Th immunity against HPV16 E7 in subjects with HPV16(+) lesions. Several of these responses matched with the 3 Th epitopes defined in our study, A numb er of other HPV16(+) subjects did not display any E7-specific type I cytoki ne-producing T-cell immunity, indicating failure of the immune response. Ou r combined data argue for more extensive as well as longitudinal analysis o f HPV16-specific T-cell immunity using the ELISPOT assay described, as well as for HPV-specific vaccination of individuals with HPV+ lesions. (C) 2001 Wiley-Liss, Inc.