Abstract
Cell-mediated immunity directed against human papillomavirus 16 (HPV-16) antigens was studied in 16 patients affected with classic vulvar intra-epithelial neoplasia (VIN), also known as bowenoid papulosis (BP). Ten patients had blood lymphocyte proliferative T cell responses directed against E6/2 (14-34) and/or E6/4 (45-68) peptides, which were identified in the present study as immunodominant among HPV-16 E6 and E7 large peptides. Ex vivo enzyme-linked immunospot-interferon (IFN)-gamma assay was positive in three patients who had proliferative responses. Twelve months later, proliferative T cell responses remained detectable in only six women and the immunodominant antigens remained the E6/2 (14-34) and E6/4 (45-68) peptides. The latter large fragments of peptides contained many epitopes able to bind to at least seven human leucocyte antigen (HLA) class I molecules and were strong binders to seven HLA-DR class II molecules. In order to build a therapeutic anti-HPV-16 vaccine, E6/2 (14-34) and E6/4 (45-68) fragments thus appear to be good candidates to increase HPV-specific effector T lymphocyte responses and clear classic VIN (BP) disease lesions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Amino Acid Sequence
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Cell Proliferation
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Epitopes, T-Lymphocyte / immunology*
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Epitopes, T-Lymphocyte / metabolism
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Female
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HLA-D Antigens / metabolism
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Histocompatibility Antigens Class I / metabolism
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Human papillomavirus 16 / immunology*
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Humans
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Interferon-gamma / metabolism
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Leukocytes, Mononuclear / cytology
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / metabolism
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Lymphocyte Activation / immunology
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Middle Aged
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Oncogene Proteins, Viral / immunology*
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Papillomavirus E7 Proteins
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Papillomavirus Infections / immunology*
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Papillomavirus Infections / virology
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Protein Binding / immunology
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Repressor Proteins / immunology*
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Time Factors
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Vulvar Neoplasms / immunology*
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Vulvar Neoplasms / virology*
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Young Adult
Substances
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E6 protein, Human papillomavirus type 16
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Epitopes, T-Lymphocyte
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HLA-D Antigens
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Histocompatibility Antigens Class I
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Oncogene Proteins, Viral
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Papillomavirus E7 Proteins
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Peptide Fragments
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Repressor Proteins
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oncogene protein E7, Human papillomavirus type 16
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Interferon-gamma