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First published on May 23, 2007; DOI: 10.1124/jpet.107.123257

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*Substance via MeSH


Received for publication March 27, 2007.
Revised April 27, 2007.
Accepted for publication May 21, 2007.

Antigen-specific suppression of experimental autoimmune encephalomyelitis by a novel bifunctional peptide inhibitor

Naoki Kobayashi 1, Hitomi Kobayashi 1, Leo Gu 2, Thomas Malefyt 2, Teruna J. Siahaan 1*

1 The University of Kansas 2 Admunex Therapeutics Inc.

* Address correspondence to: E-mail: siahaan{at}ku.edu

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. PLP-BPI was designed by conjugating two peptides, an encephalitogenic epitope of proteolipid protein (PLP139-151) and an ICAM-1-binding peptide derived from {alpha}L integrin (CD11a237-246), 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, PLP139-151 peptide only, CD11a237-246 peptide only, unlinked mixture of PLP139-151 and CD11a237-246 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 PLP139-151-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.


Key words: ICAM-1, anaphylaxis, bifunctional peptide inhibitor, experimental autoimmune encephalomyelitis, immunological synapse, peptide


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[Abstract] [Full Text] [PDF]


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