Abstract
Murine experimental allergic encephalomyelitis (EAE) is a useful model for the demyelinating, autoimmune disease multiple sclerosis. In the EAE system, the immunodominant N-terminal epitope of myelin basic protein (MBP) is an unusually short, weakly binding peptide antigen which elicits highly biased TCR chain usage. In the 2.2 A crystal structure of I-A(u)/MBP1-11 complex, only MBP residues 1-7 are bound toward one end of the peptide binding cleft. The fourth residue of MBP1-11 is located in an incompatible p6 pocket of I-A(u), thus explaining the short half-life of I-A(u) complexed with Ac1-11. MBP peptides extended at the C terminus of Ac1-11 result in dramatic affinity increases, likely attributed to register shifting to a higher affinity cryptic epitope, which could potentially mask the presentation of the immunodominant MBP1-11 peptide during thymic education.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylation
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Amino Acid Sequence
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Animals
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Antigen Presentation
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Arginine / chemistry
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Autoimmunity
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Binding Sites
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Epitopes, T-Lymphocyte / chemistry
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Epitopes, T-Lymphocyte / immunology
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Epitopes, T-Lymphocyte / metabolism
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Histocompatibility Antigens Class II / chemistry
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Histocompatibility Antigens Class II / metabolism*
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Hybridomas
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Immunodominant Epitopes / chemistry*
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Immunodominant Epitopes / immunology*
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Immunodominant Epitopes / metabolism
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Lymphocyte Activation
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Macromolecular Substances
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Mice
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Models, Molecular*
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Molecular Sequence Data
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Myelin Basic Protein / chemistry*
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Myelin Basic Protein / immunology*
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Myelin Basic Protein / metabolism
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Peptide Fragments / chemistry*
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Peptide Fragments / immunology*
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Peptide Fragments / metabolism
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Protein Binding
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Sequence Alignment
Substances
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens Class II
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Immunodominant Epitopes
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Macromolecular Substances
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Myelin Basic Protein
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Peptide Fragments
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myelin basic protein 1-11
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Arginine