Abstract
T cell-mediated destruction of the myelin sheath causes inflammatory damage of the CNS in multiple sclerosis (MS). The major T and B cell responses in MS patients who are HLA-DR2 (about two-thirds of MS patients) react to a region between residues 84 and 103 of myelin basic protein (1 ). The crystal structure of HLA-DR2 complexed with myelin basic protein(84-102) confirmed that Lys(91) is the major TCR contact site, whereas Phe(90) is a major anchor to MHC and binds the hydrophobic P4 pocket (2 ). We have tested peptides containing repetitive 4-aa sequences designed to bind critical MHC pockets and to interfere with T cell activation. One such sequence, EYYKEYYKEYYK, ameliorates experimental autoimmune encephalomyelitis in Lewis rats, an animal model of MS.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / pharmacology
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Amino Acid Sequence
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Animals
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Binding Sites / genetics
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Encephalomyelitis, Autoimmune, Experimental / drug therapy
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Female
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HLA-DR2 Antigen / metabolism
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Histocompatibility Antigens / metabolism*
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Histocompatibility Antigens Class II / metabolism
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Humans
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Models, Molecular
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Molecular Sequence Data
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Multiple Sclerosis / drug therapy
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Multiple Sclerosis / immunology
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Myelin Basic Protein / genetics
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Myelin Basic Protein / immunology
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Myelin Basic Protein / pharmacology
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Peptide Fragments / genetics
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Peptide Fragments / immunology
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Peptide Fragments / pharmacology
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Peptides / genetics
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Peptides / immunology*
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Peptides / pharmacology
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Rats
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Rats, Inbred Lew
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Receptors, Antigen, T-Cell / metabolism*
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Sequence Homology, Amino Acid
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T-Lymphocytes / immunology
Substances
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Adjuvants, Immunologic
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HLA-DR2 Antigen
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Histocompatibility Antigens
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Histocompatibility Antigens Class II
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Myelin Basic Protein
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Peptide Fragments
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Peptides
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Receptors, Antigen, T-Cell