Prevention of experimental encephalomyelitis with peptides that block interaction of T cells with major histocompatibility complex proteins.
Two synthetic immunodominant and nonencephalitogenic peptides of myelin basic protein, N1-20 and AcN9-20, effectively compete with an encephalitogenic peptide, AcN1-11, in an in vitro T-cell response restricted by class II major histocompatibility complex products (I-Au). These mutant peptide constructs, which do not occur in nature, also compete with the self-antigen for the in vivo induction of T cells primed with the encephalitogen AcN1-11. By using these nonpathogenic competitor peptides, it is possible to prevent the development of a prototypic T-cell-mediated autoimmune disease, experimental allergic encephalomyelitis. These results suggest possibilities for the utilization of competitor peptides for therapy of T-cell-mediated autoimmune diseases linked to specific major histocompatibility complex genes.
Sakai
K
K
Department of Neurology and Genetics, Stanford University, CA 94305.
Zamvil
S S
SS
Mitchell
D J
DJ
Hodgkinson
S
S
Rothbard
J B
JB
Steinman
L
L
D000595:Amino Acid Sequence; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007167:Immunotherapy; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010455:Peptides