By combining the existing quantitative bio-assays, genetics, and serology of cellular immunology with the biochemical approaches and methodologies of glycoconjugates biochemistry, we are investigating the importance of cell-surface and extracellular glycosyl moieties in the cellular interactions which regulate both the development and expression of the immune response. Since previous studies indicate that both asparagine-linked oligosaccharides and proteoglycans may play important roles in mediating lymphocyte cellular interactions, we plan to systematically investigate the biosynthesis and functions of these glycosyl moieties in thymic lymphocytes.
The specific aims of this proposal are: 1) The characterization of proteoglycans synthesized by lymphocytes. 2) The characterization of the reticulo-epithelial cellular components of the thymus, with respect to their biological properties and the types of glycoconjugates they synthesize. 3) The analysis of saccharide structural variability at individual glycosylation sites on important lymphocyte differentiation or histocompatability antigens, as a function of cellular phenotype or stage of development. 4) The """"""""mapping"""""""" of the cell-surface saccharide topography of developing or functional subsets of lymphocytes, using highly-purified glycosyltransferases as impermeant probes. 5) The continued use of the mixed-lymphocyte assay to directly ascertain the functional roles of glycosyl moieties in lymphocyte cellular interactions. These studies are providing valuable information with respect to the biochemistry and functions of important lymphocyte glycoconjugates. Clearly, the etiology of abnormal cellular behavior, such as cancer and immune or developmental dysfunction cannot be understood until we appreciate the molecular basis for its regulation in normal cells.
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