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

S H van der Burg; M E Ressing; K M Kwappenberg; A de Jong; K Straathof; J de Jong; A Geluk; K E van Meijgaarden; K L Franken; T H Ottenhoff; G J Fleuren; G Kenter; C J Melief; R Offringa

doi:10.1002/1097-0215(200002)9999:9999<::aid-ijc1119>3.0.co;2-c

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

Int J Cancer. 2001 Mar 1;91(5):612-8. doi: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1119>3.0.co;2-c.

Authors

S H van der Burg¹, M E Ressing, K M Kwappenberg, A de Jong, K Straathof, J de Jong, A Geluk, K E van Meijgaarden, K L Franken, T H Ottenhoff, G J Fleuren, G Kenter, C J Melief, R Offringa

Affiliation

¹ Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. [email protected]

PMID: 11267969
DOI: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1119>3.0.co;2-c

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-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 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cancer Vaccines
Carcinoma / chemistry
Cell Division
Cells, Cultured
Cytokines / metabolism
Epitope Mapping
Epitopes / chemistry
Female
Genes, MHC Class II
HLA-DQ Antigens / chemistry
HLA-DR Antigens / chemistry
HLA-DR Serological Subtypes
HLA-DR3 Antigen / chemistry
Humans
Immunologic Memory
Immunophenotyping
Inhibitory Concentration 50
Interferon-gamma / metabolism
Leukocytes, Mononuclear / metabolism
Major Histocompatibility Complex*
Oncogene Proteins, Viral / chemistry
Oncogene Proteins, Viral / immunology*
Papillomavirus E7 Proteins
Peptides / chemistry
Peptides / metabolism
Protein Binding
Protein Structure, Tertiary
Recombinant Proteins / metabolism
Recurrence
T-Lymphocytes, Helper-Inducer / chemistry
T-Lymphocytes, Helper-Inducer / immunology*
T-Lymphocytes, Helper-Inducer / metabolism*
Uterine Cervical Neoplasms / chemistry
Uterine Cervical Neoplasms / virology*

Substances

Cancer Vaccines
Cytokines
Epitopes
HLA-DQ Antigens
HLA-DQ2 antigen
HLA-DR Antigens
HLA-DR Serological Subtypes
HLA-DR15 antigen
HLA-DR3 Antigen
Oncogene Proteins, Viral
Papillomavirus E7 Proteins
Peptides
Recombinant Proteins
oncogene protein E7, Human papillomavirus type 16
Interferon-gamma