Antigen presentation in teleost fish: consequences of a divergent evolutionary path

这项研究建议重点研究鱼类，特别是对水产养殖重要的物种，如大西洋鲑鱼和虹鲑鱼，它们用来启动抵抗疾病的免疫反应的过程。这里研究的主要过程是抗原呈递，即提取病原体的蛋白质片段并将它们呈递给免疫系统细胞，免疫系统细胞激活对病原体的反应。对这一过程的理解在人类中得到了很好的理解，并导致了非常成功的疫苗的开发。然而，它在鱼类身上还没有得到很好的研究。因此，利用针对相关蛋白质产生的抗体，我将研究哪些蛋白质与其他蛋白质相互作用，以及在哺乳动物中执行这些功能的相同蛋白质是否与鱼类有关。我还将研究启动这种反应的刺激因素、编码蛋白质的基因的启动方式以及环境对这些基因表达的影响。最后，我的实验室将从鱼类免疫系统使用的病原体中分离出小的蛋白质片段，以了解病原体的哪些部分启动了这些反应。这项研究之所以重要，有两个原因。首先，鱼类免疫系统的进化与人类免疫系统不同，因此了解这一进化过程对于了解鱼类免疫的许多其他方面至关重要。其次，由于这种不同的进化路径和鱼类免疫系统工作的不同方式，对鱼类免疫机制和它们在这里收集的目标病原体部分的详细知识对于设计对鱼类有效的疫苗至关重要。这对水产养殖业很重要，因为目前基于哺乳动物免疫模型的疫苗并不像应有的那样有效，每年造成数百万美元的损失。这一知识也将有利于选择性亲鱼用于水产养殖业，以及用于休闲捕鱼或维持野生种群的湖泊中的鱼类放养，为加拿大的经济、环境和整个社会提供好处。

This research proposal focuses on the processes fish, in particular species important for aquaculture such as Atlantic salmon and rainbow trout, use to start immune responses which resist disease. The main process examined here, antigen presentation, takes protein fragments of pathogens and presents them to immune system cells, which activate responses to the pathogen. Understanding this process is well understood in humans and has led to the development of tremendously successful vaccines. Yet it has not been well studied in fish. Therefore, using antibodies raised against the proteins involved, I will examine which proteins interact with which others and whether or not the same proteins which carry out these functions in mammals are involved in fish. I will also examine the stimuli which initiate this response, the way in which the genes encoding the proteins are turned on and environmental influences on the expression of those genes. Finally, my laboratory will isolate the small protein fragments from the pathogens which are used by the fish immune system to understand which parts of the pathogens start these responses. This research is important for two reasons. Firstly, fish immune systems have evolved differently than human immune systems, so it is critical to understand that evolutionary process in order to understand many other aspects of fish immunity. Secondly, because of this divergent evolutionary path and the different manner in which fish immune systems work, the detailed knowledge of the mechanisms of fish immunity and the parts of the pathogen which they target gathered here is critical for the design of vaccines which work effectively in fish. This is important for the aquaculture industry as current vaccines based on mammalian immune models are not as effective as they could be, causing losses of millions of dollars each year. This knowledge will also be beneficial for selective broodstock for the aquaculture industry and for stocking of fish in lakes used for recreational fishing or maintaining wild populations, providing benefits for the Canadian economy, environment and society at large.