Human papillomavirus 16-specific T cell responses in classic HPV-related vulvar intra-epithelial neoplasia. Determination of strongly immunogenic regions from E6 and E7 proteins.
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.
Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Département d'Immunologie, Hôpital Cochin, Paris, France. isabelle.bourgault@inserm.fr
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I
Bourgault Villada
M
M
Moyal Barracco
S
S
Berville
M L
ML
Bafounta
C
C
Longvert
V
V
Prémel
P
P
Villefroy
E
E
Jullian
T
T
Clerici
B
B
Paniel
B
B
Maillère
J
J
Choppin
J G
JG
Guillet
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D049109:Cell Proliferation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006681:HLA-D Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D012097:Repressor Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014846:Vulvar Neoplasms / Q000276:immunology* / Q000821:virology*; D055815:Young Adult
C068651:E6 protein, Human papillomavirus type 16; D018984:Epitopes, T-Lymphocyte; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010446:Peptide Fragments; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma