Experimental Allergic Encephalomyelitis (EAE) is a cell-mediated, autoimmune and demyelinating disease of the central nervous system which is similar to Multiple Sclerosis in man. The major thrust of this research is to define the amino acid sequence which activates lymphocytes responsible for control and arrest of the demyelinating process. Previously, we reported that EAE may be prevented, suppressed or arrested by an antigen-specific and cyclophosphamide sensitive T lymphocyte subpopulation which we designated suppressor T lymphocytes (Ts). The development of Ts followed the administration of synthetic analogues of the disease-inducing determinants for rabbits, rats or guinea pigs. We now plan to further these studies of antigen-induced unresponsiveness to encephalitogenic challenge using specific determinants both for inducing and regulating EAE. And to define better the mechanism underlying EAE regulation. We propose, as a working hypothesis, that EAE regulation is mediated by a suppressor T lymphocyte subset that may be activated by a specific sequence, namely, the modified non-encephalitogenic sequence of the EAE-inducing determinant. To this end, we propose to synthesize a series of peptides made up of 1, 2, or 3 determinants known to induce EAE in one of 3 species. The sequence and position of these determinants mimics their respective locations in the parent MBP. Their ability to induce, regulate and/or potentiate either development or regulation of EAE in the Lewis rat will be documented by the results of this study. The successful completion of these studies is expected to provide a rational and direct approach for the control and arrest of similar demyelinating disease, such as Multiple Sclerosis in man.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021466-03
Application #
3402601
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1984-12-01
Project End
1988-02-29
Budget Start
1986-12-01
Budget End
1988-02-29
Support Year
3
Fiscal Year
1987
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
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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
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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

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