Analysis of HLA-DRB1*0901-binding HPV-16 E7 helper T cell epitope.
OBJECTIVE
This study sought to determine the human papillomavirus (HPV)-16 E7 epitopes that would be presented by HLA-DR molecules to CD4-positive T cells in patients with cervical carcinoma.


METHODS
HLA-DR binding assays were performed using HPV-16 E7-derived synthetic peptides and, after incubation with these DR-binding peptides, helper T cell frequencies were analyzed in patients whose HLA and HPV genotypes were confirmed.


RESULTS
We determined that the E7d peptide, 61CDSTLRLCVQSTHVDIRTL80E, was bound by HLA-DRB1*0901. An increased frequency (0.3-2.4%) of type 2 helper T cell responses was found in HLA-DRB1*0901-positive patients with cervical dysplasia and carcinoma. We found that when IL-12 was combined with E7d-peptide stimulation in vitro, the frequency of type 1 helper T cell responses also increased in patients with carcinoma.


CONCLUSIONS
Thus HPV-16 E7d peptide as an HLA-DRB1*0901-restricted helper T cell epitope might usefully be incorporated into an understanding of the immunological mechanism and immunotherapy for this disease.
Okubo
Mitsuo
M
Transfusion Medicine and Cell Therapy, Saitama Medical Center, Saitama Medical School, Saitama, Japan. mitokubo@saitama-med.ac.jp
Saito
Maki
M
Inoku
Hiroki
H
Hirata
Ranko
R
Yanagisawa
Masami
M
Takeda
Satoru
S
Kinoshita
Katsuyuki
K
Maeda
Hiroo
H
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D027383:Papillomaviridae; D050725:Papillomavirus E7 Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000821:virology
D004279:DNA, Viral; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C487381:HLA-DRB1*09:01 antigen; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D018664:Interleukin-12