NSF Award
9316468
9316468 McKinney Sharks evolved more than 300 million years ago, and have remained a relatively successful species. Animals live for more than 75 years in the wild and are not subject to overwhelming infectious disease in captivity. Yet, their immune system, by mammalian standards, appears to be very limited. Although antibody responses occur and non-specific cytotoxic cells are present, there has been no direct demonstration of T lymphocytes, which initiate and effect cellular immunity in more evolved vertebrates. The goal of this project is to characterize T lymphocytes in sharks, if they exist. Both cellular and molecular approaches will be taken. Using cognate antigens, antigen-reactive lymphocyte populations will be identified in sharks. In addition, the role of class II MHC molecules in their reactivity will be investigated using class II- specific cDNA and a monoclonal antibody. Three molecules characteristic of T lymphocytes will be used as tools to identify and isolate T cells: interleukin 2, perforin, and the T cell receptor. The major approach will use PCR amplification of phylogenetically conserved gene sequences coupled with cell fractionation. Lastly, the cytotoxic lymphocyte-like cell will be identified using electron microscopy. This study will determine whether T cells had evolved by the time of emergence of sharks, and may begin to clarify the origins of the adaptive immune system. %%% Sharks evolved more than 300 million years ago, and have remained a relatively successful species. Animals live for more than 75 years in the wild and are not subject to overwhelming infectious disease in captivity. Yet, their immune system, by mammalian standards, appears to be very limited. Although antibody responses occur and non-specific cytotoxic cells are present, there has been no direct demonstration of T lymphocytes, which initiate and effect cellular immunity in more evolved vertebrates. The long term goals of this laboratory are to define and understand normal immune function in the shark, to explore the natural history of the vertebrate immune system, and to determine the immune functions which permit this primitive vertebrate a relatively disease-free existence even though it apparently lacks the complexity of the mammalian host defense system. The goal of this project is to determine whether sharks have T lymphocytes and if so to identify and characterize them. The results of this research will contribute to our fundamental knowledge of the natural defense mechanisms of an organism that occupies an important place in the evolution of immune function in vertebrate species. Knowledge such as this should contribute in the long term to our ability to maintain biodiversity. ***
