REVERSAL OF ACUTE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AND PREVENTION OF RELAPSES BY TREATMENT WITH A MYELIN BASIC-PROTEIN PEPTIDE ANALOG MODIFIED TO FORM LONG-LIVED PEPTIDE-MHC COMPLEXES

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disea se induced by immunization with myelin basic protein (MBP), proteolipi d protein, or encephalitogenic peptides from these myelin components. EAE resembles multiple sclerosis in some of its clinical and histologi c features, and serves as an experimental model for this and other aut oimmune diseases. In this study, we examine i.v. peptide therapy of EA E in detail, and show that repeated i.v. injections of MBP peptides ef fectively treat EAE in (PLJ x SJL)F-1 mice. In this study, administrat ion of the immunodominant epitope (MBP Ac1-11) prevents MBP-induced di sease, whereas the subdominant epitope MBP 31-47 is neither required n or sufficient. Intravenous administration of substituted MBP peptide a nalogues is also effective in treating EAE, provided the peptide side chains presumed to be involved in TCR contact and MHC binding are pres erved. A substituted MBP peptide analogue that forms long-lived peptid e-MHC complexes in vivo is more effective than the unmodified MBP pept ide. Lower doses of the substituted peptide analogue are effective, an d the effect is longer lasting than treatment with the unmodified pept ide. Clinical signs of EAE are reversed by injection of the substitute d peptide during the acute phase of disease. Moreover, treatment of mi ce in the remission phase of EAE results in a dramatically reduced inc idence of relapse. In summary, we have shown that EAE can be reversed after onset and treated during remission with an MBP peptide analogue that has been modified for improved therapeutic potency.