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.
Transfusion Medicine and Cell Therapy, Saitama Medical Center, Saitama Medical School, Saitama, Japan. mitokubo@saitama-med.ac.jp
Mitsuo
M
Okubo
Maki
M
Saito
Hiroki
H
Inoku
Ranko
R
Hirata
Masami
M
Yanagisawa
Satoru
S
Takeda
Katsuyuki
K
Kinoshita
Hiroo
H
Maeda
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