SHORT PEPTIDE-BASED TOLEROGENS WITHOUT SELF-ANTIGENIC OR PATHOGENIC ACTIVITY REVERSE AUTOIMMUNE-DISEASE

An immunodominant epitope of myelin basic protein (MBP), VHFFKNIVTPRTP (p87-99), is a major target of T cells in brain lesions of multiple s clerosis (MS), and this peptide can trigger experimental autoimmune en cephalomyelitis (EAE). We designed truncated peptides based on this pa thogenic 13-mer that are not antigenic. These short peptides reduced p roduction of IFN-gamma and TNF-alpha in vivo. Moreover, paraplegic rat s given the 7-mer FKNIVTP in soluble form showed total reversal of par alysis in 24 h. Truncated peptides that are too small to stimulate ant igenic responses to pathogenic regions of myelin basic protein are nev ertheless effective tolerogens and are able to anergize autoreactive T cells. Short peptide-based tolerogens, devoid of immunogenic and path ogenic potential, may be attractive for therapy of autoimmune diseases .