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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI017712-07
Application #
3127404
Study Section
Experimental Immunology Study Section (EI)
Project Start
1980-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Qiu, J X; Marcus, D M (1999) Use of peptide ligands to analyze the fine specificity of antibodies against asialo GM1. J Neuroimmunol 100:58-63
Qiu, J X; Kai, M; Padlan, E A et al. (1999) Structure-function studies of an anti-asialo GM1 antibody obtained from a phage display library. J Neuroimmunol 97:172-81
Gillard, B K; Clement, R G; Marcus, D M (1998) Variations among cell lines in the synthesis of sphingolipids in de novo and recycling pathways. Glycobiology 8:885-90
Dinh, Q; Weng, N P; Kiso, M et al. (1996) High affinity antibodies against Lex and sialyl Lex from a phage display library. J Immunol 157:732-8
Gillard, B K; Harrell, R G; Marcus, D M (1996) Pathways of glycosphingolipid biosynthesis in SW13 cells in the presence and absence of vimentin intermediate filaments. Glycobiology 6:33-42
Marcus, D M; Weng, N (1994) The structure of human anti-ganglioside antibodies. Prog Brain Res 101:289-93
Gillard, B K; Thurmon, L T; Harrell, R G et al. (1994) Biosynthesis of glycosphingolipids is reduced in the absence of a vimentin intermediate filament network. J Cell Sci 107 ( Pt 12):3545-55
Weng, N P; Ritter, E; Yucel, E et al. (1994) Specificity and structure of murine monoclonal antibodies against GM1 ganglioside. J Neuroimmunol 55:61-8
Snyder, J G; Dinh, Q; Morrison, S L et al. (1994) Structure-function studies of anti-3-fucosyllactosamine (Le(x)) and galactosylgloboside antibodies. J Immunol 153:1161-70
Gillard, B K; Thurmon, L T; Marcus, D M (1993) Variable subcellular localization of glycosphingolipids. Glycobiology 3:57-67

Showing the most recent 10 out of 32 publications