Origins of T Helper Cell Function in Adaptive Immunity

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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.