Glycosphingolipids (GSLs) are complex lipids that are immunogens, receptors and markers of celulr differentiation. Recent data suggest that they may also have immunoregulatory properties. Glycolipids occur in cell membranes and lipoproteins, and some GSL antigens of erythrocytes and lymphocytes are acquired from plasman lipoproteins and not synthesized in situ. The first section of this grant concerns the immunoregulatory properties of GSLs and their transfer from lipopritens to lymphocytes and erthrocytes. The objectives of this work are: (1) to determine the quantity of glycolipid which each major clas of lipoprotein can transfer to lymphocytes, and to examine the kinetics, mechanism and reversibility of this process; (2) to evaluate the role of glycolipids in the immunoregulatory activity of lipoproteins; and (3) to ascertain if the plasma of cancer patients contains different glycolipids than normal plasma, and if the lipoproteins of cancer patients are more immunosuppressive than normal lipoproteins. The second section of this grant includes several studies of GSL immunology and biochemicstry. The objectives of these projects are: (1) to determine the structures of human blood group Lua and Lub antigens; (2) to determine the GSL composition and immunological expression of human erythroid cels at various stages of differentiation; (3) to analyxe the immuno response to gangliosides of patients with a number of diseases which involve the central nervous system; and (4) to develop more sensitive and specific techniques for immunochemical analyses of GSLs. We will develop highly specific antibodies. We will develop highly specific antibodies to erythrocyte blood group and differentiation antigens that will be useful for blood typing, for analysis of erythroid and myeloid leukemias, and for detection of human antigens on somatic cell hybrids.
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