The purpose of this study is to define the immunological properties of bovine peripheral nerve myelin P2 protein, especially with regard to its ability to produce experimental allergic neuritis (EAN) in Lewis rats. By isolating immunogenic peptide fragments, we will localize the antigenic and neuritogenic determinants, and investigate the properties of these determinants. Using the P2 protein we will attempt to manipulate the immune response so as to affect and particularly to treat the disorder. We will also investigate the role of lymphocyte subsets in EAN by using monoclonal antibodies that define these subsets. We will investigate the ability of the monoclonal antibodies to affect the course of EAN produced both by active sensitization and by transfer of activated cells. We will study the role played by these lymphocyte subsets during transfer of EAN by treating donor cells with the monoclonal antibodies or by depleting various subpopulations by rosetting using monoclonal antibodies that define these subsets. We will also develop T cell lines that mediate EAN and study the effect of the monoclonal antibodies on the ability of the T cell lines to produce EAN. We will attempt to develop monoclonal antibodies to the T cell lines which can alter the course of EAN. We will also use the T cell lines to help define the neuritogenic determinant(s) of the P2 protein. We hope to be able to learn the best way to treat EAN with monoclonal antibodies and/or peptides in order to stop the disease or promote recovery. Since experimental allergic neuritis is the appropriate animal model for human idiopathic polyneuritis, we hope that this information can serve as a basis from which one can devise similar treatments of relevant human demyelinating diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS011867-17
Application #
3394644
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1977-05-01
Project End
1992-07-31
Budget Start
1990-08-01
Budget End
1992-07-31
Support Year
17
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Powell, H C; Myers, R R; Mizisin, A P et al. (1991) Response of the axon and barrier endothelium to experimental allergic neuritis induced by autoreactive T cell lines. Acta Neuropathol 82:364-77
Powell, H C; Olee, T; Brostoff, S W et al. (1991) Comparative histology of experimental allergic neuritis induced with minimum length neuritogenic peptides by adoptive transfer with sensitized cells or direct sensitization. J Neuropathol Exp Neurol 50:658-74
Olee, T; Powell, H C; Brostoff, S W (1990) New minimum length requirement for a T cell epitope for experimental allergic neuritis. J Neuroimmunol 27:187-90
Ellerman, K; Brostoff, S (1988) A suppressor cell line that prevents the adoptive transfer of EAE in Lewis rats. Ann N Y Acad Sci 540:364-6
Brostoff, S W; White, T M; Powers, J M (1988) Treatment of clinical experimental allergic encephalomyelitis in the rat using fragments and combinations of monoclonal antibodies. J Neuroimmunol 17:167-73
Olee, T; Powers, J M; Brostoff, S W (1988) A T cell epitope for experimental allergic neuritis. J Neuroimmunol 19:167-73
Weise, M J; Carnegie, P R (1988) An approach to searching protein sequences for superfamily relationships or chance similarities relevant to the molecular mimicry hypothesis: application to the basic proteins of myelin. J Neurochem 51:1267-73
Sedgwick, J; Brostoff, S; Mason, D (1987) Experimental allergic encephalomyelitis in the absence of a classical delayed-type hypersensitivity reaction. Severe paralytic disease correlates with the presence of interleukin 2 receptor-positive cells infiltrating the central nervous system. J Exp Med 165:1058-75
Robinson, A P; White, T M; Mason, D W (1986) Macrophage heterogeneity in the rat as delineated by two monoclonal antibodies MRC OX-41 and MRC OX-42, the latter recognizing complement receptor type 3. Immunology 57:239-47
Robinson, A P; White, T M; Mason, D W (1986) MRC OX-43: a monoclonal antibody which reacts with all vascular endothelium in the rat except that of brain capillaries. Immunology 57:231-7

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