Proliferative T cell responses to human papillomavirus type 16 L1 peptides in patients with cervical dysplasia.
Identifieur interne : 003E14 ( Main/Exploration ); précédent : 003E13; suivant : 003E15Proliferative T cell responses to human papillomavirus type 16 L1 peptides in patients with cervical dysplasia.
Auteurs : P S Shepherd [Royaume-Uni] ; A J Rowe ; J C Cridland ; T. Coletart ; P. Wilson ; J C LuxtonSource :
- The Journal of general virology [ 0022-1317 ] ; 1996.
Descripteurs français
- KwdFr :
- ADN viral (analyse), Activation des lymphocytes, Antigènes viraux (immunologie), Biopsie, Capside (immunologie), Cartographie épitopique, Col de l'utérus (anatomopathologie), Col de l'utérus (virologie), Données de séquences moléculaires, Dysplasie du col utérin (anatomopathologie), Dysplasie du col utérin (immunologie), Dysplasie du col utérin (virologie), Femelle, Humains, Lignée cellulaire, Lymphocytes T (cytologie), Lymphocytes T (immunologie), Néoplasie intraépithéliale cervicale (anatomopathologie), Néoplasie intraépithéliale cervicale (immunologie), Néoplasie intraépithéliale cervicale (virologie), Papillomaviridae (génétique), Papillomaviridae (immunologie), Protéines de capside, Protéines des oncogènes viraux (immunologie), Protéines des oncogènes viraux (synthèse chimique), Séquence d'acides aminés, Techniques de culture, Tumeurs du col de l'utérus (anatomopathologie), Tumeurs du col de l'utérus (immunologie), Tumeurs du col de l'utérus (virologie), Études transversales.
- MESH :
- analyse : ADN viral.
- anatomopathologie : Col de l'utérus, Dysplasie du col utérin, Néoplasie intraépithéliale cervicale, Tumeurs du col de l'utérus.
- cytologie : Lymphocytes T.
- génétique : Papillomaviridae.
- immunologie : Antigènes viraux, Capside, Dysplasie du col utérin, Lymphocytes T, Néoplasie intraépithéliale cervicale, Papillomaviridae, Protéines des oncogènes viraux, Tumeurs du col de l'utérus.
- synthèse chimique : Protéines des oncogènes viraux.
- virologie : Col de l'utérus, Dysplasie du col utérin, Néoplasie intraépithéliale cervicale, Tumeurs du col de l'utérus.
- Activation des lymphocytes, Biopsie, Cartographie épitopique, Données de séquences moléculaires, Femelle, Humains, Lignée cellulaire, Protéines de capside, Séquence d'acides aminés, Techniques de culture, Études transversales.
English descriptors
- KwdEn :
- Amino Acid Sequence, Antigens, Viral (immunology), Biopsy, Capsid (immunology), Capsid Proteins, Cell Line, Cervical Intraepithelial Neoplasia (immunology), Cervical Intraepithelial Neoplasia (pathology), Cervical Intraepithelial Neoplasia (virology), Cervix Uteri (pathology), Cervix Uteri (virology), Cross-Sectional Studies, Culture Techniques, DNA, Viral (analysis), Epitope Mapping, Female, Humans, Lymphocyte Activation, Molecular Sequence Data, Oncogene Proteins, Viral (chemical synthesis), Oncogene Proteins, Viral (immunology), Papillomaviridae (genetics), Papillomaviridae (immunology), T-Lymphocytes (cytology), T-Lymphocytes (immunology), Uterine Cervical Dysplasia (immunology), Uterine Cervical Dysplasia (pathology), Uterine Cervical Dysplasia (virology), Uterine Cervical Neoplasms (immunology), Uterine Cervical Neoplasms (pathology), Uterine Cervical Neoplasms (virology).
- MESH :
- chemical , analysis : DNA, Viral.
- chemical , chemical synthesis : Oncogene Proteins, Viral.
- chemical , immunology : Antigens, Viral, Oncogene Proteins, Viral.
- cytology : T-Lymphocytes.
- genetics : Papillomaviridae.
- immunology : Capsid, Cervical Intraepithelial Neoplasia, Papillomaviridae, T-Lymphocytes, Uterine Cervical Dysplasia, Uterine Cervical Neoplasms.
- pathology : Cervical Intraepithelial Neoplasia, Cervix Uteri, Uterine Cervical Dysplasia, Uterine Cervical Neoplasms.
- virology : Cervical Intraepithelial Neoplasia, Cervix Uteri, Uterine Cervical Dysplasia, Uterine Cervical Neoplasms.
- Amino Acid Sequence, Biopsy, Capsid Proteins, Cell Line, Cross-Sectional Studies, Culture Techniques, Epitope Mapping, Female, Humans, Lymphocyte Activation, Molecular Sequence Data.
Abstract
Human papillomavirus type 16 (HPV-16) can cause genital warts, cervical dysplasias and carcinoma of the cervix. Cell-mediated immunity is thought to be important in protection against the virus and in its elimination, but little is known about the mechanisms involved. In a cross-sectional study we have demonstrated proliferative T cell responses to peptides representing the HPV-16 L1 capsid protein (aa 199-409) in the peripheral blood of 63% of patients (n = 41) with histological evidence of cervical dysplasia and in 45% of healthy age-matched controls (n = 11). This was achieved by generating short-term T cell lines (STLs) from each individual in vitro against a beta-galactosidase-HPV- 16 L1 (aa 199-409) fusion protein for 2 weeks, and then identifying the HPV epitopes they recognized with overlapping synthetic peptides (15-mers) spanning this region in 3 day specificity assays. Histological grading and HPV typing by PCR were performed on patients' cervical biopsies taken at the same clinical visit as the peripheral blood samples. An immunogenic region was identified between aa 311-345 in 73% of patients (18% in controls) who responded to HPV-16 L1 (aa 199-409). The number of responders to this region was significantly higher in patients with HPV-16-positive biopsies when compared to those with HPV-16-negative biopsies (P = 0.006), as was the number of responders to individual peptides 311-325 (NLASSNYFPTPSGSM; p = 0.04) and 321-335 (PSGSMVTSDAQIFNK; P = 0.004) representing this region. The mean level of response to each individual peptide was also higher in the patient group than the controls (P < 0.05). The most significant finding was that all patients with evidence of a current HPV-16 infection responded to one or more L1 peptides (P = 0.0004) and 92% had high grade cervical intraepithelial neoplasia (CIN III). We also found that the CIN III group was more likely to respond to any L1 peptide than either the atypical group (P = 0.04) or the controls (P = 0.05). Data from four individuals showed that the majority of peptide-specific STLs were CD4+ but some CD8+ STLs were also detected.
DOI: 10.1099/0022-1317-77-4-593
PubMed: 8627247
Affiliations:
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Coletart</name></author><author><name sortKey="Wilson, P" sort="Wilson, P" uniqKey="Wilson P" first="P" last="Wilson">P. Wilson</name></author><author><name sortKey="Luxton, J C" sort="Luxton, J C" uniqKey="Luxton J" first="J C" last="Luxton">J C Luxton</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1996">1996</date><idno type="RBID">pubmed:8627247</idno><idno type="pmid">8627247</idno><idno type="doi">10.1099/0022-1317-77-4-593</idno><idno type="wicri:Area/PubMed/Corpus">002780</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002780</idno><idno type="wicri:Area/PubMed/Curation">002780</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002780</idno><idno type="wicri:Area/PubMed/Checkpoint">002613</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002613</idno><idno type="wicri:Area/Ncbi/Merge">002A15</idno><idno type="wicri:Area/Ncbi/Curation">002A15</idno><idno type="wicri:Area/Ncbi/Checkpoint">002A15</idno><idno type="wicri:doubleKey">0022-1317:1996:Shepherd P:proliferative:t:cell</idno><idno type="wicri:Area/Main/Merge">003E69</idno><idno type="wicri:Area/Main/Curation">003E14</idno><idno type="wicri:Area/Main/Exploration">003E14</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Proliferative T cell responses to human papillomavirus type 16 L1 peptides in patients with cervical dysplasia.</title><author><name sortKey="Shepherd, P S" sort="Shepherd, P S" uniqKey="Shepherd P" first="P S" last="Shepherd">P S Shepherd</name><affiliation wicri:level="3"><nlm:affiliation>Department of Immunology, Guy's Hospital Medical School, UMDS, London, UK. p.shepherd@uk.ac.umds.miranda</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Immunology, Guy's Hospital Medical School, UMDS, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Rowe, A J" sort="Rowe, A J" uniqKey="Rowe A" first="A J" last="Rowe">A J Rowe</name></author><author><name sortKey="Cridland, J C" sort="Cridland, J C" uniqKey="Cridland J" first="J C" last="Cridland">J C Cridland</name></author><author><name sortKey="Coletart, T" sort="Coletart, T" uniqKey="Coletart T" first="T" last="Coletart">T. Coletart</name></author><author><name sortKey="Wilson, P" sort="Wilson, P" uniqKey="Wilson P" first="P" last="Wilson">P. Wilson</name></author><author><name sortKey="Luxton, J C" sort="Luxton, J C" uniqKey="Luxton J" first="J C" last="Luxton">J C Luxton</name></author></analytic><series><title level="j">The Journal of general virology</title><idno type="ISSN">0022-1317</idno><imprint><date when="1996" type="published">1996</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Antigens, Viral (immunology)</term><term>Biopsy</term><term>Capsid (immunology)</term><term>Capsid Proteins</term><term>Cell Line</term><term>Cervical Intraepithelial Neoplasia (immunology)</term><term>Cervical Intraepithelial Neoplasia (pathology)</term><term>Cervical Intraepithelial Neoplasia (virology)</term><term>Cervix Uteri (pathology)</term><term>Cervix Uteri (virology)</term><term>Cross-Sectional Studies</term><term>Culture Techniques</term><term>DNA, Viral (analysis)</term><term>Epitope Mapping</term><term>Female</term><term>Humans</term><term>Lymphocyte Activation</term><term>Molecular Sequence Data</term><term>Oncogene Proteins, Viral (chemical synthesis)</term><term>Oncogene Proteins, Viral (immunology)</term><term>Papillomaviridae (genetics)</term><term>Papillomaviridae (immunology)</term><term>T-Lymphocytes (cytology)</term><term>T-Lymphocytes (immunology)</term><term>Uterine Cervical Dysplasia (immunology)</term><term>Uterine Cervical Dysplasia (pathology)</term><term>Uterine Cervical Dysplasia (virology)</term><term>Uterine Cervical Neoplasms (immunology)</term><term>Uterine Cervical Neoplasms (pathology)</term><term>Uterine Cervical Neoplasms (virology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN viral (analyse)</term><term>Activation des lymphocytes</term><term>Antigènes viraux (immunologie)</term><term>Biopsie</term><term>Capside (immunologie)</term><term>Cartographie épitopique</term><term>Col de l'utérus (anatomopathologie)</term><term>Col de l'utérus (virologie)</term><term>Données de séquences moléculaires</term><term>Dysplasie du col utérin (anatomopathologie)</term><term>Dysplasie du col utérin (immunologie)</term><term>Dysplasie du col utérin (virologie)</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire</term><term>Lymphocytes T (cytologie)</term><term>Lymphocytes T (immunologie)</term><term>Néoplasie intraépithéliale cervicale (anatomopathologie)</term><term>Néoplasie intraépithéliale cervicale (immunologie)</term><term>Néoplasie intraépithéliale cervicale (virologie)</term><term>Papillomaviridae (génétique)</term><term>Papillomaviridae (immunologie)</term><term>Protéines de capside</term><term>Protéines des oncogènes viraux (immunologie)</term><term>Protéines des oncogènes viraux (synthèse chimique)</term><term>Séquence d'acides aminés</term><term>Techniques de culture</term><term>Tumeurs du col de l'utérus (anatomopathologie)</term><term>Tumeurs du col de l'utérus (immunologie)</term><term>Tumeurs du col de l'utérus (virologie)</term><term>Études transversales</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>DNA, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Oncogene Proteins, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens, Viral</term><term>Oncogene Proteins, Viral</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>ADN viral</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Col de l'utérus</term><term>Dysplasie du col utérin</term><term>Néoplasie intraépithéliale cervicale</term><term>Tumeurs du col de l'utérus</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Lymphocytes T</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>T-Lymphocytes</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Papillomaviridae</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Papillomaviridae</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes viraux</term><term>Capside</term><term>Dysplasie du col utérin</term><term>Lymphocytes T</term><term>Néoplasie intraépithéliale cervicale</term><term>Papillomaviridae</term><term>Protéines des oncogènes viraux</term><term>Tumeurs du col de l'utérus</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Capsid</term><term>Cervical Intraepithelial Neoplasia</term><term>Papillomaviridae</term><term>T-Lymphocytes</term><term>Uterine Cervical Dysplasia</term><term>Uterine Cervical Neoplasms</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Cervical Intraepithelial Neoplasia</term><term>Cervix Uteri</term><term>Uterine Cervical Dysplasia</term><term>Uterine Cervical Neoplasms</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Protéines des oncogènes viraux</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Col de l'utérus</term><term>Dysplasie du col utérin</term><term>Néoplasie intraépithéliale cervicale</term><term>Tumeurs du col de l'utérus</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Cervical Intraepithelial Neoplasia</term><term>Cervix Uteri</term><term>Uterine Cervical Dysplasia</term><term>Uterine Cervical Neoplasms</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Biopsy</term><term>Capsid Proteins</term><term>Cell Line</term><term>Cross-Sectional Studies</term><term>Culture Techniques</term><term>Epitope Mapping</term><term>Female</term><term>Humans</term><term>Lymphocyte Activation</term><term>Molecular Sequence Data</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Activation des lymphocytes</term><term>Biopsie</term><term>Cartographie épitopique</term><term>Données de séquences moléculaires</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire</term><term>Protéines de capside</term><term>Séquence d'acides aminés</term><term>Techniques de culture</term><term>Études transversales</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Human papillomavirus type 16 (HPV-16) can cause genital warts, cervical dysplasias and carcinoma of the cervix. Cell-mediated immunity is thought to be important in protection against the virus and in its elimination, but little is known about the mechanisms involved. In a cross-sectional study we have demonstrated proliferative T cell responses to peptides representing the HPV-16 L1 capsid protein (aa 199-409) in the peripheral blood of 63% of patients (n = 41) with histological evidence of cervical dysplasia and in 45% of healthy age-matched controls (n = 11). This was achieved by generating short-term T cell lines (STLs) from each individual in vitro against a beta-galactosidase-HPV- 16 L1 (aa 199-409) fusion protein for 2 weeks, and then identifying the HPV epitopes they recognized with overlapping synthetic peptides (15-mers) spanning this region in 3 day specificity assays. Histological grading and HPV typing by PCR were performed on patients' cervical biopsies taken at the same clinical visit as the peripheral blood samples. An immunogenic region was identified between aa 311-345 in 73% of patients (18% in controls) who responded to HPV-16 L1 (aa 199-409). The number of responders to this region was significantly higher in patients with HPV-16-positive biopsies when compared to those with HPV-16-negative biopsies (P = 0.006), as was the number of responders to individual peptides 311-325 (NLASSNYFPTPSGSM; p = 0.04) and 321-335 (PSGSMVTSDAQIFNK; P = 0.004) representing this region. The mean level of response to each individual peptide was also higher in the patient group than the controls (P < 0.05). The most significant finding was that all patients with evidence of a current HPV-16 infection responded to one or more L1 peptides (P = 0.0004) and 92% had high grade cervical intraepithelial neoplasia (CIN III). We also found that the CIN III group was more likely to respond to any L1 peptide than either the atypical group (P = 0.04) or the controls (P = 0.05). Data from four individuals showed that the majority of peptide-specific STLs were CD4+ but some CD8+ STLs were also detected.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Londres</li></region><settlement><li>Londres</li></settlement></list><tree><noCountry><name sortKey="Coletart, T" sort="Coletart, T" uniqKey="Coletart T" first="T" last="Coletart">T. Coletart</name><name sortKey="Cridland, J C" sort="Cridland, J C" uniqKey="Cridland J" first="J C" last="Cridland">J C Cridland</name><name sortKey="Luxton, J C" sort="Luxton, J C" uniqKey="Luxton J" first="J C" last="Luxton">J C Luxton</name><name sortKey="Rowe, A J" sort="Rowe, A J" uniqKey="Rowe A" first="A J" last="Rowe">A J Rowe</name><name sortKey="Wilson, P" sort="Wilson, P" uniqKey="Wilson P" first="P" last="Wilson">P. Wilson</name></noCountry><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Shepherd, P S" sort="Shepherd, P S" uniqKey="Shepherd P" first="P S" last="Shepherd">P S Shepherd</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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