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

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 ( PLP139-151) 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 PLP139-151, 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.