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

脊椎动物的免疫系统保护个体免受疾病和肿瘤的侵害。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，但对低等脊椎动物（如鱼类）的免疫库发育过程知之甚少。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t细胞和辅助性t细胞来源于一个共同的t细胞前体，在胸腺中通过一个称为t细胞发育的过程接受特定的信号后，该前体承诺这两个谱系中的任何一个。人们提出了两种不同的模型来解释哺乳动物的t细胞发育。本研究的目的是研究虹鳟鱼的这一过程，为研究这两种模型提供一种比较方法。本研究将评估导致鱼类中两种t细胞亚群发育的途径和信号。具体来说，该提案将允许开发工具，如单克隆抗体，可用于跟踪鳟鱼t细胞在其发育过程中利用的发育程序。该项目还将用于培养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最新技术。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。总的来说，该项目的主要目标是提供对鱼类中控制t细胞发育过程的基本了解，并确定所有脊椎动物中该过程的保护程度。这些研究将对处理哺乳动物t细胞发育的研究产生影响，同时也为鲑鱼的保存和维护提供基础研究和工具。

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.