Analysis of HLA-DRB1^*O901-binding HPV-16 E7 Helper T cell Epitope.

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Objective : This study sought to determine the human papillomavirus(HPV)-16E7 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 and Conclusion : We determined that the E7d peptide,^<61>CDSTLRLCVQSTHVDIRTL^<80>E, 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 dyaplasia and carcinoma. We found that when IL-12 was combined with E7d-peptide stimulation in vitro, the frequency of type 1helper T cell responses also increased in the patients with carcinoma. Thus HPV-16 E7d peptide as an HLA-DRB1^*0901-restricted helper T cell epitope might usefully be incorporated in understanding immunological mechanism and immunotherapy for this disease.