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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
Author(s) -
van der Burg Sjoerd H.,
Ressing Maaike E.,
Kwappenberg Kitty M.C.,
de Jong Annemieke,
Straathof Karin,
de Jong Joan,
Geluk Annemieke,
van Meijgaarden Krista E.,
Franken Kees L.M.C.,
Ottenhoff Tom H.M.,
Fleuren Gert Jan,
Kenter Gemma,
Melief Cornelis J.M.,
Offringa Rienk
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200002)9999:9999<::aid-ijc1119>3.0.co;2-c
Subject(s) - elispot , epitope , immunology , immunity , biology , antigen , immune system , virology , cellular immunity , human leukocyte antigen , t cell
Abstract Tumor‐specific T‐helper (Th) immunity was found to play a pivotal role in the natural and vaccine‐induced immune defense against tumors. Since the majority of cervical cancers express human papillomavirus type 16 (HPV16) E7 oncoprotein, it is important to investigate the Th response against this target antigen in detail. By means of PBMC cultures from HLA‐typed healthy donors, we identified the central part of HPV16 E7 (E7 41–72 ) as the major immunogenic 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‐γ 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 number of other HPV16 + subjects did not display any E7‐specific type 1 cytokine‐producing T‐cell immunity, indicating failure of the immune response. Our combined data argue for more extensive as well as longitudinal analysis of HPV16‐specific T‐cell immunity using the ELISPOT assay described, as well as for HPV‐specific vaccination of individuals with HPV + lesions. © 2001 Wiley‐Liss, Inc.