Abstract
The small heat shock protein alphaB-crystallin is considered as a candidate autoantigen in multiple sclerosis (MS) lesions. Gelatinase B or matrix metalloproteinase (MMP)-9 is a proteinase establishing various disease-promoting feedback loops in autoimmune diseases. Human alphaB-crystallin was digested with natural gelatinase B and all cleavage sites were identified by a combined approach of mass spectrometry and peptide sequencing analysis. Previously identified immunodominant and cryptic epitopes of alphaB-crystallin in mice and rats were generated and largely left intact by MMP-9 processing. The alphaB-crystallin peptide 1-16, generated as a remnant epitope, provoked a significant T cell response in alphaB-crystallin knockout mice. None of the remnant peptides was encephalitogenic when injected intracerebrally into mice or induced MMP-9 in vitro. Gelatinase B is thus able to release T cell epitopes from intact alphaB-crystallin, but their pathogenic role remains unclear.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Line, Tumor
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Epitopes, T-Lymphocyte / metabolism*
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Epitopes, T-Lymphocyte / pharmacology
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Humans
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Hydrolysis
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Injections, Intraventricular
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Lymphocyte Activation / immunology
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Matrix Metalloproteinase 9 / metabolism
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Matrix Metalloproteinase 9 / physiology*
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Matrix Metalloproteinase Inhibitors*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Sequence Data
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Multiple Sclerosis / enzymology*
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Multiple Sclerosis / immunology*
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
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Rats
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Rats, Inbred Lew
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Recombinant Proteins / metabolism
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology
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alpha-Crystallin B Chain / administration & dosage
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alpha-Crystallin B Chain / genetics
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alpha-Crystallin B Chain / metabolism*
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alpha-Crystallin B Chain / pharmacology
Substances
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Epitopes, T-Lymphocyte
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Matrix Metalloproteinase Inhibitors
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Peptide Fragments
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Recombinant Proteins
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alpha-Crystallin B Chain
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Matrix Metalloproteinase 9