There is a growing body of evidence demonstrating that information carried by carbohydrate groups of lymphocyte glycoproteins and glycolipids play important roles cellular communication by these cells. Indeed, there are now well documented examples of carbohydrate binding proteins (CBPs) that are either expressed on or bind to lymphocytes and mediate defined functions including lymphocyte trafficking, apoptosis, and cytokine production. There is also clear but fragmentary evidence that glycosylation is dynamically regulated during lymphocyte differentiation and activation. Many of the CBPs involved in lymphocyte biology recognize either sialic containing carbohydrates or their 'asialo' core structures. This project is focused on the regulated expression of this large class of carbohydrates through the action of sialyltransferases, sialidases and other glycosyltransferases. Elucidation of the regulation of sialoside expression will lead to a deeper understanding of how CBPs of known function are modulated by their ligands, and is expected to help elucidate the functions of many other CBPs whose functions are not yet known.The major objectives of the project are to directed to 1) define the temporal changes in sialic acid containing carbohydrates of B cells, CD4+ T cells, and CD8+ T cells following their activation and differentiation, 2) establish which enzymes regulate the glycosylation changes, and at what level that regulation is exerted, and 3) investigate the role of the carbohydrate ligand of CD22 as a modulator of B cell signaling. The primary focus will be to study glycosylation changes following activation of lymphocytes, and how these changes relate to B cell and T cell function.
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