Lectins have been used widely as a probe for study of cell surface saccharides although the specificities of lectins is too broad to specify a definite carbohydrate structure on the cell surface. Furthermore, lectins are multivalent, difficult to convert into a monovalent state, they are, therefore, pinocytocyzed rapidly by cells, and express various cytotoxicities. In contrast, the anti-carbohydrate antibody directed against a defined single carbohydrate structure of a glycolipid or oligosaccharide derivative shows narrow specificity, no demonstrable cytotoxicity, and is readily converted to a monovalent fragment (Fab). This proposal includes: 1. Extensive studies on basic conditions for preparation of and general properties of a large variety of monospecific anti-carbohydrate antibodies, and 2. use of such antibodies and their monovalent derivatives in various cell biological studies: a) determination of the quantity and the quality of various saccharides on cell surfaces and in intracellular membranes as related to animal cell functions (cell contact, cell proliferation, etc,) b) effect of multivalent and monovalent antibodies on surface functions and c) effect of purified anti-carbohydrate antibodies on lymphocyte mediated immune reaction such as blocking of target cell destruction. The approach will be useful in solving various problems in cell biology, particularly the control mechanism of cell proliferation through membrane-saccharides.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM023100-09
Application #
3271493
Study Section
Cognition and Perception Study Section (CP)
Project Start
1976-05-01
Project End
1986-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
9
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
Tsuruoka, T; Tsuji, T; Nojiri, H et al. (1993) Selection of a mutant cell line based on differential expression of glycosphingolipid, utilizing anti-lactosylceramide antibody and complement. J Biol Chem 268:2211-6
Fenderson, B A; Ostrander, G K; Hausken, Z et al. (1992) A ceramide analogue (PDMP) inhibits glycolipid synthesis in fish embryos. Exp Cell Res 198:362-6
Andrews, P W; Nudelman, E; Hakomori, S et al. (1990) Different patterns of glycolipid antigens are expressed following differentiation of TERA-2 human embryonal carcinoma cells induced by retinoic acid, hexamethylene bisacetamide (HMBA) or bromodeoxyuridine (BUdR). Differentiation 43:131-8
Felding-Habermann, B; Igarashi, Y; Fenderson, B A et al. (1990) A ceramide analogue inhibits T cell proliferative response through inhibition of glycosphingolipid synthesis and enhancement of N,N-dimethylsphingosine synthesis. Biochemistry 29:6314-22
Eggens, I; Fenderson, B; Toyokuni, T et al. (1989) Specific interaction between Lex and Lex determinants. A possible basis for cell recognition in preimplantation embryos and in embryonal carcinoma cells. J Biol Chem 264:9476-84
Andrews, P W; Gonczol, E; Fenderson, B A et al. (1989) Human cytomegalovirus induces stage-specific embryonic antigen 1 in differentiating human teratocarcinoma cells and fibroblasts. J Exp Med 169:1347-59
Chen, C; Fenderson, B A; Andrews, P W et al. (1989) Glycolipid glycosyltransferases in human embryonal carcinoma cells during retinoic acid induced differentiation. Biochemistry 28:2229-38
Inoue, H; Hirohashi, S; Shimosato, Y et al. (1989) Establishment of an anti-A human monoclonal antibody from a blood group A lung cancer patient: evidence for the occurrence of autoimmune response to difucosylated type-2 chain A. Eur J Immunol 19:2197-203
Kojima, N; Hakomori, S (1989) Specific interaction between gangliotriaosylceramide (Gg3) and sialosyllactosylceramide (GM3) as a basis for specific cellular recognition between lymphoma and melanoma cells. J Biol Chem 264:20159-62
Eggens, I; Fenderson, B A; Toyokuni, T et al. (1989) A role of carbohydrate-carbohydrate interaction in the process of specific cell recognition during embryogenesis and organogenesis: a preliminary note. Biochem Biophys Res Commun 158:913-20

Showing the most recent 10 out of 30 publications