ROLE OF T CELL EPITOPES IN TUMOR SURVEILLANCE

T 细胞表位在肿瘤监测中的作用

• 批准号: 3197059
• 负责人: Denis James Moss
• 金额: $ 10.28万
• 依托单位: QUEENSLAND INSTITUTE OF MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3197059
• 关键词: Epstein Barr virus; Herpesviridae vaccine; cell mediated lymphocytolysis test; colony stimulating factor; cytotoxic T lymphocyte; epitope mapping; human subject; latent virus infection; neoplasm /cancer vaccine; polymerase chain reaction; site directed mutagenesis; transforming virus; tumor antigens; viral carcinogenesis; virus protein

Our long-term aim is to provide an in-depth understanding of the relationship between Epstein-Barr virus (EBV) and human disease as a basis of formulating an intervention strategy. Compelling evidence has demonstrated that EBV persists for life following primary infection and is controlled by EBV-specific cytotoxic T lymphocytes (CTLs). Disruption of this delicate balance between virus and host results in an expansion of virus-infected cells which may contribute to a spectrum of clinical disorders including malignancy. The theme of this proposal is to exploit our expertise in the mapping of CTL epitopes and in EBV strain variation to establish a frame of reference to developing a vaccine capable of preventing EBV-associated diseases. Specifically, we propose to: (1)identify the dominant and secondary EBV CTL epitopes using procedures already in use in our laboratories. The techniques involved include T-cell colony formation, Cr release assay, site directed mutagenesis and gene targeting of proteins in transformation and T-cell recognition. (2)determine the extent of EBV strain variation, in particular the variation associated with CTL epitopes. (3)to define the importance of CTL epitopes in the recognition of associated tumors.

我们的长期目标是深入了解 爱泼斯坦-巴尔病毒（EBV）与人类疾病之间的关系作为基础 制定干预策略。令人信服的证据有 证明 EBV 在初次感染后会终生持续存在，并且 由 EBV 特异性细胞毒性 T 淋巴细胞 (CTL) 控制。扰乱 病毒和宿主之间的这种微妙平衡导致 病毒感染的细胞可能会导致一系列临床症状 疾病，包括恶性肿瘤。本提案的主题是利用 我们在 CTL 表位定位和 EBV 毒株变异方面的专业知识 建立一个开发疫苗的参考框架 预防 EB 病毒相关疾病。具体来说，我们建议： (1)使用程序识别显性和次要 EBV CTL 表位 已经在我们的实验室中使用。涉及的技术包括T细胞 集落形成、Cr 释放测定、定点诱变和基因 转化和 T 细胞识别中的蛋白质靶向。 (2)确定EBV毒株变异的程度，特别是 与CTL表位相关的变异。 (3)定义CTL表位在识别中的重要性 相关肿瘤。