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

HLA-DRB1^*O901 结合 HPV-16 E7 辅助 T 细胞表位分析。

• 批准号: 13670472
• 负责人: OKUBO Mitsuo
• 金额: $ 1.98万
• 依托单位: Saitama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670472/
• 关键词: HLA-DR; T cell epitope; human papillomavirus; Th1, Th2; cervical carcinoma; 子宮癌; Th1; Th2; ヒトパピローマウイルス; HLA; T細胞

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.

目的：本研究旨在确定人乳头瘤病毒（HPV）-16E7表位，这些表位将由HLA-DR分子呈递给宫颈癌患者的CD 4阳性T细胞。使用HPV-16 E7衍生的合成肽进行HLA-DR结合测定，并且在与这些DR结合肽孵育后，结果和结论：我们确定了E7 d肽^<61>CDSTLRLCVQSTHVDIRTL^<80>E与HLA-DRB 1 ^*0901结合。在HLA-DRB 1 ^*0901阳性的宫颈不典型增生和宫颈癌患者中，发现2型辅助性T细胞反应的频率增加（0.3-2.4%）。我们发现，当IL-12与E7 d-肽在体外联合刺激时，肿瘤患者的1型辅助性T细胞应答频率也增加。因此，HPV-16 E7 d肽作为HLA-DRB 1 ^*0901限制性辅助性T细胞表位可能有助于了解这种疾病的免疫机制和免疫治疗。

项目成果

Mitsuo Okubo, Maki Saito, Hiroki Inoku, Ranko Hirata, Masami Yanagisawa, Satoru Takeda, Katsuyuki Kinoshita, Hiroo.: "Analysis of HLA-DRB1^*0901-binding HPV-16 E7 Helper T cell Epitope."Journal of Obstetrics and Gynaecology Research. 30(in press). 120-129

Mitsuo Okubo、Maki Saito、Hiroki Inoku、Ranko Hirata、Masami Yanagisawa、Satoru Takeda、Katsuyuki Kinoshita、Hiroo.：“HLA-DRB1^*0901 结合 HPV-16 E7 辅助 T 细胞表位的分析。”妇产科杂志

Mitsuo Okubo, Maki Saito, Hiroki Inoku, Ranko Hirata, Masami Yanagisawa, Satoru Takeda, Katsuyuki Kinoshita, Hiroo Maeda.: "Analysis of HLA-DRB1^*0901-binding HPV-16 E7 Helper T cell Epitope."Journal of Obstetrics and Gynaecology Research. 30. 120-129 (20

Mitsuo Okubo、Maki Saito、Hiroki Inoku、Ranko Hirata、Masami Yanagisawa、Satoru Takeda、Katsuyuki Kinoshita、Hiroo Maeda.：“HLA-DRB1^*0901 结合 HPV-16 E7 辅助 T 细胞表位的分析。”妇产科杂志

Mitsuo Okubo, Maki Saito, Hiroki Inoku, Ranko Hirata, Masami Yanagisawa, Satoru Takeda, Katsuyuki Kinoshita, Hiroo Maeda: "Analysis of HLA-DRB1^*0901-binding HPV-16 E7 Helper T cell Epitope."Journal of Obstetrics and Gynaecology Research. 30. 120-129 (200

Mitsuo Okubo、Maki Saito、Hiroki Inoku、Ranko Hirata、Masami Yanagisawa、Satoru Takeda、Katsuyuki Kinoshita、Hiroo Maeda：“分析 HLA-DRB1^*0901 结合 HPV-16 E7 辅助 T 细胞表位。”妇产科杂志