Experimental Allergic Encephalomyelitis (EAE) is a cell-mediated, autoimmune and demyelinating disease of the central nervous system. The disease is similar to multiple sclerosis in man. In the past, research was focused on myelin basic protein (MBP), fragments derived from it, and their respective immunological activity. An exciting development in our laboratory has been the recent demonstration in Lewis rats that the encephalitogenic sequence of synthetic peptide S49S (residues 69-84 of the MBP) houses T cell and B cell epitopes, none of which alone induces EAE. However, antibodies prepared against the C-terminal region of S49S potentiate the cell-mediated immune response to the N-terminal region of the same peptide leading to the development of EAE.
The aims of the proposed research are: To prepare monoclonal antibodies against the S49S sequence using the hybridoma technology; to define the sequence boundaries and synthesize the B cell and T cell epitopes known to be present in the S49S; and to study the role of each of the anti-S49S monoclonal antibodies in the development and proliferation of specific T effector cells in autoimmune demyelination in the Lewis rat. It is anticipated that the successful completion of these studies will provide valuable information that will help elucidate the mechanism underlying EAE and clarify the role of specific antibodies in the development of disease, thus providing new insights for the control and arrest of similar demyelinating diseases in man.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021466-05
Application #
3402602
Study Section
Neurology C Study Section (NEUC)
Project Start
1984-12-01
Project End
1992-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
St. Luke's Roosevelt Hosp Center (New York)
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10025
Bourdette, D N; Chou, Y K; Whitham, R H et al. (1998) Immunity to T cell receptor peptides in multiple sclerosis. III. Preferential immunogenicity of complementarity-determining region 2 peptides from disease-associated T cell receptor BV genes. J Immunol 161:1034-44
Bourdette, D N; Whitham, R H; Chou, Y K et al. (1994) Immunity to TCR peptides in multiple sclerosis. I. Successful immunization of patients with synthetic V beta 5.2 and V beta 6.1 CDR2 peptides. J Immunol 152:2510-9
Chou, Y K; Jones, R E; Bourdette, D et al. (1994) Human myelin basic protein (MBP) epitopes recognized by mouse MBP-selected T cell lines from multiple sclerosis patients. J Neuroimmunol 49:45-50
Satyanarayana, K; Chou, Y K; Bourdette, D et al. (1993) Epitope specificity and V gene expression of cerebrospinal fluid T cells specific for intact versus cryptic epitopes of myelin basic protein. J Neuroimmunol 44:57-67
Vandenbark, A A; Bourdette, D N; Whitham, R et al. (1993) T-cell receptor peptide therapy in EAE and MS. Clin Exp Rheumatol 11 Suppl 8:S51-3
Vandenbark, A A; Hashim, G; Offner, H (1993) TCR peptide therapy in autoimmune diseases. Int Rev Immunol 9:251-76
Chou, Y K; Bourdette, D N; Offner, H et al. (1992) Frequency of T cells specific for myelin basic protein and myelin proteolipid protein in blood and cerebrospinal fluid in multiple sclerosis. J Neuroimmunol 38:105-13
Chou, Y K; Henderikx, P; Jones, R E et al. (1992) Human CD8+ T cell clone regulates autologous CD4+ myelin basic protein specific T cells. Autoimmunity 14:111-9
Vandenbark, A A; Chou, Y K; Bourdette, D N et al. (1992) T cell receptor peptide therapy for autoimmune disease. J Autoimmun 5 Suppl A:83-92
Vainiene, M; Gold, D P; Celnik, B et al. (1992) Common sequence on distinct V beta genes defines a protective idiotope in experimental encephalomyelitis. J Neurosci Res 31:413-20

Showing the most recent 10 out of 44 publications