Monoclonal antibodies to dopaminergic (D2) and serotoninergic (S2) drugs (neuroleptics) and receptors will be made using the strategy of idiotype: anti-idiotype molecular mimicry. This strategy employs an antibody (idiotype) directed against D2 or S2 antagonists (ligands) to act as a """"""""mold"""""""" for the subsequent production of an anti-idiotype antibody which can constitute an """"""""internal image"""""""" of the anti-ligand binding site, and thereby mimic, in molecular terms, the original ligand. A collection of monoclonal antibodies to the dopaminergic ligands haloperidol and pimozide have been produced and subsequent anti-idiotype antibodies are currently being tested. These receptor binding antibodies will be used in receptor characterization, localization and purification studies. These studies will provide valuable information tools for the study of idiotype:anti-idiotype mimicry and the role of anti-receptor antibodies in nervous system diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022448-02
Application #
3404834
Study Section
Neurology C Study Section (NEUC)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Kussie, P H; Albright, G; Linthicum, D S (1989) Production and characterization of monoclonal idiotypes and anti-idiotypes for small ligands. Methods Enzymol 178:49-63
Kussie, P H; Sherman, M A; Marchetti, D et al. (1989) Molecular analysis of monoclonal idiotypes and anti-idiotypes. Methods Enzymol 178:91-107
Linthicum, D S; Bolger, M B; Kussie, P H et al. (1988) Analysis of idiotypic and anti-idiotypic antibodies as models of receptor and ligand. Clin Chem 34:1676-80
Sherman, M A; Deans, R J; Bolger, M B (1988) Haloperidol binding to monoclonal antibodies. Hypervariable region amino acid sequence determination. J Biol Chem 263:4059-63
Sherman, M A; Bolger, M B (1988) Haloperidol binding to monoclonal antibodies. Predictions of three-dimensional combining site structure via computer modeling. J Biol Chem 263:4064-74
Hall, E R; Lane, C L; Linthicum, D S (1987) Monoclonal antibody against TXB2: its use in solid and liquid phase radioimmunoassays. Prostaglandins Leukot Med 30:103-9
Sherman, M A; Linthicum, D S; Bolger, M B (1986) Haloperidol binding to monoclonal antibodies: conformational analysis and relationships to D-2 receptor binding. Mol Pharmacol 29:589-98
Simmons, R D; Linthicum, D S (1986) A simple 'free 3H-ligand' assay for rapid screening of hybridoma monoclonal antibodies against neurotransmitter analogs and anti-idiotype antibodies. J Neuroimmunol 11:245-9
Linthicum, D S; Bolger, M B (1985) Using molecular mimicry to produce anti-receptor antibodies. Bioessays 3:213-7