Adaptive antiviral cell-meditaed immune reactions agäinst IHNV in rainbow trout (Oncorhynchus mykiss)

虹鳟 (Oncorhynchus mykiss) 中针对 IHNV 的适应性抗病毒细胞介导的免疫反应

• 批准号: 126382186
• 负责人: Privatdozent Dr. Uwe Fischer
• 金额: --
• 依托单位: Institut für Infektionsmedizin (IMED)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/126382186?language=en
• 关键词: Adaptive; antiviral; cell; meditaed; immune

Cell-mediated cytotoxicity (CMC) is an important immune response mechanism in virus-infected hosts. Viruses replicate intracellularly and their proteins are cleaved by the host cell's proteasome to peptides that can be bound to MHC class I/beta2m monomers. This complex is finally presented on the host`s cell surface to the T cell receptors (TCR) of cytotoxic T lymphocytes (CTLs) triggering clonal expansion of antigen-specific CTLs. These mechanisms are likely to exist in fish because homologues of the main molecules involved in MHC class I loading and presentation have been discovered. Also, functional studies on the effector mechanisms lead to this suggestion. A significant part of these data were obtained in the laboratory of the applicant and his collaborators. However, in fish there is no information available yet on viral peptides presented by infected cells, nor do tools exist for CTL labelling. Knowledge on these immune response mechanisms will be extremely useful to understand the mechanisms of antiviral immune responses especially in the commercial fish species rainbow trout and for economically important viral infections such as infectious haematopoietic necrosis (IHNV).An aim of the initial project was:I. Analysis of viral peptides presented by MHC class I molecules on IHNV infected trout cells.For this, MHC class I presented IHNV-derived peptides were predicted and their capacity to stabilize recombinant MHC class I and beta2m protein complexes.The remaining aim of the renewal proposal will be: II. Analysis and characterization of IHNV-specific cytotoxic cells using virus-peptide loaded MHC class I tetramers.Fluorescence labelled in vitro synthesized MHC class I/beta2m tetramers loaded with the synthetic peptides will be used for the identification and separation of IHNV peptide-specific CTLs to study their gene expression profile, homing and cytotoxic properties. In conclusion, detailed knowledge of antiviral cell-mediated immune reactions in rainbow trout will give further insight into the evolution of the vertebrate immune system (1), add to the understanding of fish immune responses (2) and will finally allow to specifically design urgently needed anti-viral vaccines in fish facilitating an efficient antigen presentation (3).

细胞介导的细胞毒性（CMC）是病毒感染宿主的重要免疫应答机制。病毒在细胞内复制，它们的蛋白质被宿主细胞的蛋白酶体切割成可以与MHC I类/β 2 m单体结合的肽。这种复合物最终在宿主细胞表面呈递给细胞毒性T淋巴细胞（CTL）的T细胞受体（TCR），引发抗原特异性CTL的克隆扩增。这些机制很可能存在于鱼类中，因为已经发现了参与MHC I类装载和呈递的主要分子的同源物。此外，效应器机制的功能研究导致这一建议。这些数据的很大一部分是在申请人及其合作者的实验室中获得的。然而，在鱼类中，还没有关于由感染细胞呈递的病毒肽的信息，也不存在用于CTL标记的工具。这些免疫反应机制的知识将是非常有用的，以了解抗病毒免疫反应的机制，特别是在商业鱼种虹鳟鱼和经济上重要的病毒感染，如传染性造血坏死（IHNV）。 分析IHNV感染的鳟鱼细胞上由MHC I类分子呈递的病毒肽。为此，预测了MHC I类呈递的IHNV衍生肽及其稳定重组MHC I类和β 2 m蛋白复合物的能力。 使用装载病毒肽的MHC I类四聚体分析和表征IHNV特异性细胞毒性细胞荧光标记的体外合成的装载有合成肽的MHC I类/β 2 m四聚体将用于鉴定和分离IHNV肽特异性CTL以研究其基因表达谱、归巢和细胞毒性特性。总之，对虹鳟鱼抗病毒细胞介导的免疫反应的详细了解将进一步了解脊椎动物免疫系统的进化（1），增加对鱼类免疫反应的了解（2），并最终允许专门设计急需的抗病毒疫苗在鱼类中促进有效的抗原呈递（3）。