Interactions of the TCR co-receptors and p56LCK in an Ectothermic Model

脊椎动物的免疫系统用来保护个体免受疾病和肿瘤的侵袭。它由先天和适应性特征组成，这些特征在哺乳动物中已经得到了很好的研究，但对鱼类等低等脊椎动物免疫系统的发育过程知之甚少。因此，鱼类模型可以为形成脊椎动物免疫系统的过程提供一个进化的视角。细胞毒性和辅助性T细胞来自一种常见的T细胞前体，该T细胞前体在胸腺通过T细胞发育过程接收特定信号后，致力于这两种谱系中的任何一种。已经提出了两种不同的模型来解释哺乳动物中T细胞的发育。这项研究的目的是研究彩虹鲑鱼的这一过程，为检验这两种模型提供一种比较的方法。这项研究将评估导致FISH中两个T细胞亚群发育的途径和信号。具体地说，这项提议将允许开发诸如克隆抗体等工具，这些工具可以用于遵循鲑鱼T细胞在发育过程中所利用的发育计划。该项目还将用于培训和教育高中生和本科生在分子生物学和免疫学方面的批判性思维和当前技术。它还将向学生展示使用比较研究来解决生物学基本范式的价值。总体而言，该项目的主要目标是提供对鱼类T细胞发育过程的基本了解，长期目标是确定这一过程在所有脊椎动物中的保护程度。这些研究将对涉及哺乳动物T细胞发育的研究产生影响，同时还提供可应用于鲑鱼保存和维护的基础研究和工具。

The vertebrate immune system serves to protect individuals from disease and neoplasm. It is composed of innate and adaptive characteristics that have been well-studied in mammals but very little is known about the processes governing the development of the immune repertoire in lower vertebrates, such as fish. Thus a fish model can provide an evolutionary perspective into the processes that have shaped the vertebrate immune system. Cytotoxic and helper T-cells are derived from a common T-cell precursor that commits to either of these two lineages after receiving specific signals in the thymus through a process known as T-cell development. Two different models have been put forth to explain T-cell development in mammals. It is the goal of this study to examine this process in rainbow trout to provide a comparative approach for examining the two models. This study will assess the pathways and signals that lead to development of the two T-cell subsets in fish. Specifically, this proposal will allow for the development of tools such as monoclonal antibodies that can be used to follow the developmental program that trout T-cells utilize during their development.This project will also serve to train and educate high school and undergraduate students in critical thought and current techniques in molecular biology and immunology. It will also show students the value of using comparative studies to solve fundamental paradigms in biology. Overall, the major objective of this project is to provide a basic understanding of the processes governing T-cell development in fish with a long-term goal of ascertaining the extent of conservation for this process in all vertebrates. These studies will have ramifications for research dealing the development of T-cells in mammals while also providing basic research and tools that can be applied to the preservation and maintenance of salmonid fish.