Induction and the epitope analysis of human T cells specitic for human papilloma virus

人乳头瘤病毒特异性T细胞的诱导和表位分析

• 批准号: 10670434
• 负责人: TSUKUI Taku
• 金额: $ 2.05万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670434/
• 关键词: Papillomavirus; Cervical cancer; T cells; oncogene; epitope; ヘルパーT細胞; キラーT細胞

In order to investigate immune surveilence system for malignant tumors, it is important to know cellular immunity specific for tumor cells. Human papillomaviruses (HPVs) an useful tool to study cellular immune response agaist viruses and cancers induced by the viruses during the chronic infection, bscause papillomaviruses is almost established to be the cause of human cervical cancers among about 70% of the patients.We tested the cytolytic T cell (CTL) response against the truncated peptides of HPV16 E6 and E7 oncogenes from peripheral blood cells of the infected subjects detected by RT-PCR analysis of cervical cells. We could detect the CTL rsponse in 5 subjects among 150 subjects in HPV16- infected subjects. We also try to detect the minimum T cell epitopes of these CTL, and determine the HLA restriction and cell surface marker of these cells. We also induced the helper T cells specific for HPV16 E6 and E7 peptides using IL-2 response as the marker, and also detected several helper T cells specific for these petides. We try to induce the specific helper and killer clones in these cells, to know the mechanisms of T cell recognition agaist the oncogene products. We would like to study the minimum epitopes of these cells and HLA restriction to investigate the pathogenesis of cervical cancer, and the possibility of peptide vaccine for cervical neoplasms.

为了研究恶性肿瘤的免疫监测系统，了解肿瘤细胞特异性的细胞免疫至关重要。人乳头瘤病毒（hpv）是研究慢性感染过程中细胞对病毒的免疫反应和病毒引起的癌症的有用工具，因为乳头瘤病毒几乎被确定是人类宫颈癌的病因，约占70%的患者。采用RT-PCR方法检测宫颈细胞中hpv16e6和E7癌基因截短肽对感染者外周血细胞的细胞溶解T细胞（CTL）反应。我们在150例HPV16感染者中检测到5例CTL反应。我们还尝试检测这些CTL的最小T细胞表位，并确定这些细胞的HLA限制性和细胞表面标记。我们还利用IL-2反应作为标记，诱导了HPV16 E6和E7肽特异性的辅助T细胞，并检测了这些肽特异性的几种辅助T细胞。我们试图在这些细胞中诱导特异性的辅助克隆和杀伤克隆，以了解T细胞识别癌基因产物的机制。我们希望通过研究这些细胞的最小表位和HLA限制来探讨宫颈癌的发病机制，以及宫颈癌肽疫苗的可能性。

项目成果

Tsukui T: "Aging increases, and duodenal ulcer reduces the risk for intestinal metaplasia of the gastric corpus in Japanese patients with dyspepsia"J.of Gastroenterol and Hepatol. 16. 15-21 (2001)

Tsukui T：“老龄化加剧，十二指肠溃疡降低了日本消化不良患者胃体肠化生的风险”J.of Gastroenterol and Hepatol。

Tsukui T: "Aging increases, and duodenal ulcer reduces the risk for intestinal metaplasia of the gastric corpus in Japanese patients with dyspepsia."J.Gastroenterol and Hepatol.. 16. 15-21 (2001)

Tsukui T：“老龄化增加，十二指肠溃疡降低了日本消化不良患者胃体肠化生的风险。”J.Gastroenterol and Hepatol.. 16. 15-21 (2001)

Tsukui T, Kashiwagi R, Sakano M et al.: "Aging intreases, and duodenal Llcer reduces the risk for intestinal motaplasia of the gastric corpus in Japanese patients with dyspepsia."J Gastroenterol Hepatol. Jan(16). 15-21 (2001)

Tsukui T、Kashiwagi R、Sakano M 等人：“衰老和十二指肠溃疡可降低日本消化不良患者胃体肠异生的风险。”J Gastroenterol Hepatol。