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
- Research Support, U.S. Gov't, Non-P.H.S.
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Adjuvants, Immunologic / pharmacology
- Amino Acid Sequence
- Animals
- Binding Sites / genetics
- Encephalomyelitis, Autoimmune, Experimental / drug therapy
- Encephalomyelitis, Autoimmune, Experimental / immunology*
- Female
- HLA-DR2 Antigen / metabolism
- Histocompatibility Antigens / metabolism*
- Histocompatibility Antigens Class II / metabolism
- Humans
- Models, Molecular
- Molecular Sequence Data
- Multiple Sclerosis / drug therapy
- Multiple Sclerosis / immunology
- Myelin Basic Protein / genetics
- Myelin Basic Protein / immunology
- Myelin Basic Protein / pharmacology
- Peptide Fragments / genetics
- Peptide Fragments / immunology
- Peptide Fragments / pharmacology
- Peptides / genetics
- Peptides / immunology*
- Peptides / pharmacology
- Rats
- Rats, Inbred Lew
- Receptors, Antigen, T-Cell / metabolism*
- Sequence Homology, Amino Acid
- T-Lymphocytes / immunology
Substances
- Adjuvants, Immunologic
- HLA-DR2 Antigen
- Histocompatibility Antigens
- Histocompatibility Antigens Class II
- Myelin Basic Protein
- Peptide Fragments
- Peptides
- Receptors, Antigen, T-Cell