Antigen recognition in autoimmune encephalomyelitis and the potential for peptide-mediated immunotherapy.
Peptide binding and lymph node T cell activation studies have been used to characterize T cell recognition of an encephalitogenic T cell autoantigen from myelin basic protein in (PL/J x SJL)F1 mice. Amino acids that determine interactions with either the restriction element of the major histocompatibility complex (MHC) or the encephalitogenic T cell receptor are defined. This information enables the design of peptides that bind MHC yet do not cross-react with the autoantigen. A peptide analog of the encephalitogenic epitope is shown to be "heteroclitic" for MHC binding and activation of encephalitogenic T cells in vitro. This analog is not immunogenic for encephalitogenic T cells in vivo and is shown to inhibit disease that is induced by the autoantigen itself.
Wraith
D C
DC
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305.
Smilek
D E
DE
Mitchell
D J
DJ
Steinman
L
L
McDevitt
H O
HO
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001324:Autoantigens / Q000276:immunology*; D002846:Chromatography, Affinity; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy; D000939:Epitopes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000302:isolation & purification; D006825:Hybridomas / Q000276:immunology; D007167:Immunotherapy; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D009842:Oligopeptides