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

目的：本研究旨在确定HLA-DR分子对宫颈癌患者cd4阳性T细胞呈递的人乳头瘤病毒(HPV)-16E7表位。方法：使用HPV-16 e7衍生的合成肽进行HLA- dr结合试验，并与这些dr结合肽孵育后，分析HLA和HPV基因型确定的患者的辅助T细胞频率。结果与结论：我们确定E7d肽^<61>CDSTLRLCVQSTHVDIRTL^<80>E与HLA-DRB1^*0901结合。HLA-DRB1^*0901阳性的宫颈发育不良和癌患者出现2型辅助性T细胞应答的频率增加（0.3-2.4%）。我们发现，当IL-12联合e7d肽刺激时，癌症患者的1型辅助性T细胞反应频率也增加。因此，hpv - 16e7d肽作为HLA-DRB1^*0901限制性辅助性T细胞表位可能有助于了解该病的免疫机制和免疫治疗。

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.