This is an interdisciplinary program of research directed toward improving blood service care for cytopenic patients through transfusion and bone marrow transplantation. The program has two foci, one on the platelet and platelet-derived growth factors (PDGF), the other on the human major histocompatibility complex (MHC) as a determinant of immunological function, including the acceptance or rejection of engrafted marrow. Studies of the platelet cytoskeleton will characterize, define the intracellular location and seek a physiological role in mature platelets and during platelet morphogenesis for a new major microtubule protein, IEF-51K. Two projects will study PDGF. One is concerned with the interrelationships between PDGF and PDGF-like molecules synthesized locally by monocytes/macrophages and by vascular endothelial cells, on the one hand, and vascular smooth muscle cells, on the other, in sites of platelet and monocyte/macrophage activation. The other project explores the mechanisms by which human T-lymphocytes undergo induction of PDGF synthesis after infection by HTLV-I or HTLV-II. The three immunogenetics projects further define the alleles and genetic markers that characterize extended haplotypes (fixed combinations of MHC alleles on the short arm of chromosome 6 that account for about 30% of haplo-types in Caucasians). This will involve analyses of genes in the region and the Class I and Class II proteins they synthesize. The extended haplotypes will be used to explore and define genes determining the antibody response to hepatitis B surface antigen and to the polysaccharide phosphate capsular antigen of H. influenzae, the number and functional activity of natural killer cells, T cell-monocyte/mac- rophage interactions in antigen presentation and in the mixed lymphocyte reaction. Thus, this program seeks to improve our ability to preserve platelets for transfusion, to better understand the role of platelets in normal and pathologic physiology, to improve our ability to identify unrelated donors for marrow transplantation, and to better understand the immune responses to blood and blood products.
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