This Program Project will investigate several areas regarding the immunobiology of natural killer cells including molecular biology of genes associated with NK differentiation and function, surface structures involved in NK recognition, cytotoxicity, adhesion and migration, and lineage analyses of NK cell differential from bone marrow progenitor cells. In a well integrated program involving strong collaborative efforts among 5 selected prinicipal investigators, specific areas of study will include the following: 1) production of monoclonal antibodies to identify surface structures important in NK and LAK cell function. These will include MoAbs reacting with lethal hit mechanisms, structures involved in growth and differentiation of NK cells in response to interleukin-2, and lineage relationships among bone marrow- derived NK progenitor cells and mature NK cells; 2) molecular biologic studies of genes implicted in determination of NK cell phenotype and function by their selective expression in NK cells or NK and T cells; 3) analysis of molecules and genes involved in NK function with genes encoding cytotoxic factors (NKCF, cytolysis) in these cells; 4) studies of growth governing the growth and differentiation of these cells and lineage relationships among NK progenitors T cells and mature LGL; 5) finally, investigations of the in vitro and in vivo adhesion and migration of NK cells, including endothelial cell adhesion, extracellular matrix interactions, production of degradative proteases and migration patterns of NK and LAK cells in vivo. The Program Project under the direction of Ronald B. Herberman will integrate the 5 areas of investigation over a 5 year period. In addition to the basic research objectives, a research and administrative core as well as a project scientific advisory group will serve to coordinate and strengthen the collaborate efforts of the program initiative. It is anticipated that information gained from this Program Project will provide needed answers to several important questions regarding the cellular and molecular biology of NK cells and will provide a strong foundation for future studies on the biology and funcitonal significance of these cells.
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