Origins of T Helper Cell Function in Adaptive Immunity

描述(申请人提供)：T淋巴细胞功能是脊椎动物适应性免疫反应的中心。尽管所有有颌骨的脊椎动物都有所需的基本抗原受体，但对鲨鱼的研究表明，与哺乳动物相比，这类最古老的群体的T细胞功能处于次优状态。Flajnik实验室的最新数据表明，护士鲨的脾白髓中实际上可能有T细胞区。我假设鲨鱼T细胞确实会激活次级淋巴组织中特定区域的B细胞，从而显示出与哺乳动物相似的T细胞解剖和生理。为了验证这一假设，我将用免疫组织化学方法识别护士鲨脾B细胞区附近区域的细胞。T细胞辅助功能的评估将通过半抗原载体结合实验进行。此外，激光捕获显微切割将进一步实现解剖和功能目标，在初级和次级淋巴组织中进行TCR转录本分析。这些研究将极大地促进我们对适应性细胞免疫学的系统发育基础方面的理解，包括T辅助细胞功能和排除T细胞介导的自身免疫。同时，这项工作将为我自己的独立研究计划做最后的准备。

DESCRIPTION (provided by applicant): T lymphocyte function is central to the vertebrate adaptive immune response. Although all jawed vertebrates have the basic antigen receptors required, studies in sharks have suggested sub-optimal T cell function in this oldest such group compared to that of mammals. Recent data from the Flajnik lab suggest that the nurse shark may in fact have T cell zones in the spleenic white pulp. I have hypothesized that shark T cells do activate B cells in specific areas of secondary lymphoid tissue, thus displaying T cell anatomy and physiology akin to that of mammals. To test this hypothesis, I will identify the cells in the area adjacent to the B cell zones of the nurse shark spleen with immunohistochemistry. Functional assessment of T cell help will be conducted with hapten carrier conjugate experiments. In addition, laser-capture microdissection will further both the anatomical and functional aims with mapped TCR transcript analysis in primary and secondary lymphoid tissue. These studies will significantly advance our understanding of the phylogenetically fundamental aspects of adaptive cellular immunology, including T helper cell function and preclusion of T cell mediated autoimmunity. Concurrently, this work will provide the final step in preparation for my own independent program of research.