Monoclonal antibodies to dopaminergic (D2) and serotoninergic (S2) receptors of the central nervous system 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 sitem 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
Modified Research Career Development Award (K04)
Project #
1K04NS000974-01
Application #
3074834
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1985-04-01
Project End
1990-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
1
Fiscal Year
1985
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; Anchin, J M; Subramaniam, S et al. (1991) Analysis of the binding site architecture of monoclonal antibodies to morphine by using competitive ligand binding and molecular modeling. J Immunol 146:4248-57
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
Simmons, R D; Buzbee, T M; Linthicum, D S (1989) Methysergide, a serotonin antagonist, does not inhibit the expression of autoimmune encephalomyelitis in the rabbit. J Neuroimmunol 22:77-9
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
Simmons, R D; Buzbee, T M; Linthicum, D S (1988) An immunohistological study of autoimmune encephalomyelitis and neuritis in the rabbit. Observations in the dorsal root ganglion using the freeze-dried paraffin-embedded tissue technique. J Neurol Sci 83:293-304
Simmons, R D; Buzbee, T M; Linthicum, D S (1987) A freeze-dried paraffin-embedded tissue technique for immunohistochemical studies requiring unfixed tissue from the nervous system. J Neurosci Methods 22:91-6
Simmons, R D; Buzbee, T M; Linthicum, D S et al. (1987) Simultaneous visualization of vascular permeability change and leukocyte egress in the central nervous system during autoimmune encephalomyelitis. Acta Neuropathol 74:191-3
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