Abstract
The objective of this study is to evaluate the activity of a novel peptide, i.e., bifunctional peptide inhibitor (BPI), which targets the immunological synapse and inhibits autoimmune responses in an antigen-specific manner. Proteolipid protein (PLP)-BPI was designed by conjugating two peptides, an encephalitogenic epitope of proteolipid protein (PLP(139-151)) and an intercellular adhesion molecule-1-binding peptide derived from alpha(L) integrin (CD11a(237-246)), via a spacer peptide. The therapeutic effect of PLP-BPI was studied in experimental autoimmune encephalomyelitis (EAE) in female SJL/J mice as a model for human multiple sclerosis. Mice that received i.v. injections of PLP-BPI showed significantly lower EAE disease scores and incidence than those treated with vehicle, PLP(139-151) peptide only, CD11a(237-246) peptide only, unlinked mixture of PLP(139-151), and CD11a(237-246) peptides, or other control peptides. Multiple injections of antigenic peptide can produce anaphylactic responses; interestingly, PLP-BPI-treated animals have significantly lower anaphylactic response than do the PLP(139-151)-treated group. Therefore, PLP-BPI can effectively inhibit the disease severity and incidence of EAE with a lower possibility of inducing fatal anaphylaxis. These results suggest that BPI-type molecules can be used to treat different autoimmune diseases in which antigenic epitopes have been identified.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Anaphylaxis / chemically induced
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Anaphylaxis / immunology
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Animals
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Antigens / chemistry
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Antigens / immunology
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Antigens / therapeutic use*
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Body Weight / drug effects
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CD11a Antigen / chemistry
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Capsid Proteins / chemistry
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Encephalomyelitis, Autoimmune, Experimental / drug therapy*
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Female
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Interferon-gamma / metabolism
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Interleukin-10 / metabolism
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Interleukin-4 / metabolism
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Mice
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Mice, Inbred Strains
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Models, Immunological
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Molecular Sequence Data
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Myelin Proteolipid Protein / chemistry
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Myelin Proteolipid Protein / immunology
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Ovalbumin / chemistry
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Peptide Fragments / chemistry
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Peptide Fragments / immunology
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Peptides / immunology
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Peptides / therapeutic use*
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Peptides / toxicity
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Spleen / cytology
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Spleen / immunology
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T-Lymphocyte Subsets / drug effects
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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Time Factors
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Transforming Growth Factor beta / metabolism
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Vaccination
Substances
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Antigens
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CD11a Antigen
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Capsid Proteins
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Myelin Proteolipid Protein
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PLP-BPI peptide
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Peptide Fragments
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Peptides
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Transforming Growth Factor beta
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VP2 protein, Theilovirus
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myelin proteolipid protein (139-151)
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Interleukin-10
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Interleukin-4
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Interferon-gamma
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Ovalbumin