Abstract
Previously, we have reported that proteolipid protein (PLP) peptide 91-110 can induce experimental autoimmune encephalomyelitis (EAE) in HLA-DR3 transgenic (tg) mice. Here we, report that residues spanning 97-108 are the minimal epitope required for induction of EAE in DR3 mice. Utilizing a series of alanine-substituted peptides, positions 99, 101, 102, 103, 104, and 106 are identified as residues necessary for an immune response. Further analysis indicated that amino acid isoleucine (99), aspartate (102) and lysine (104) are anchor residues facilitating binding to HLA-DR3 molecules. These results may have applications in the future design of peptide based immunotherapy.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alanine / immunology
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Animals
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Apoproteins / chemistry
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Apoproteins / toxicity*
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Brain / drug effects
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Brain / metabolism
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Brain / pathology
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Cell Proliferation / drug effects
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Cytokines / metabolism
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Encephalomyelitis, Autoimmune, Experimental / chemically induced*
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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HLA-DR3 Antigen / genetics
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HLA-DR3 Antigen / immunology*
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Humans
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Immunization, Passive
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Immunodominant Epitopes / chemistry
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Immunodominant Epitopes / immunology*
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Immunodominant Epitopes / toxicity
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Major Histocompatibility Complex / physiology
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Mice
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Mice, Transgenic
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Models, Immunological
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Myelin Proteolipid Protein / chemistry
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Myelin Proteolipid Protein / toxicity*
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Peptide Fragments / immunology
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Peptide Fragments / toxicity
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Receptors, Antigen, T-Cell / metabolism
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Spinal Cord / drug effects
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Spinal Cord / metabolism
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Spinal Cord / pathology
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T-Lymphocytes / immunology*
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Time Factors
Substances
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Apoproteins
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Cytokines
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HLA-DR3 Antigen
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Immunodominant Epitopes
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Myelin Proteolipid Protein
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Alanine