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 sclerosis (MS), and this peptide can trigger experimental autoimmune encephalomyelitis (EAE). We designed truncated peptides based on this pathogenic 13-mer that are not antigenic. These short peptides reduced production of IFN-gamma and TNF-alpha in vivo. Moreover, paraplegic rats given the 7-mer FKNIVTP in soluble form showed total reversal of paralysis in 24 h. Truncated peptides that are too small to stimulate antigenic responses to pathogenic regions of myelin basic protein are nevertheless effective tolerogens and are able to anergize autoreactive T cells. Short peptide-based tolerogens, devoid of immunogenic and pathogenic potential, may be attractive for therapy of autoimmune diseases.
Karin
N
N
Department of Neurology and Neurological Sciences, Beckman Center for Molecular and Genetic Medicine-B002, Stanford University School of Medicine, CA 94305, USA.
Binah
O
O
Grabie
N
N
Mitchell
D J
DJ
Felzen
B
B
Solomon
M D
MD
Conlon
P
P
Gaur
A
A
Ling
N
N
Steinman
L
L
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000628:therapy*; D005260:Female; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000502:physiology; D004676:Myelin Basic Protein / Q000276:immunology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D004676:Myelin Basic Protein; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma