T cell recognition in experimental autoimmune encephalomyelitis: prospects for immune intervention with synthetic peptides.
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 mice of the H-2u haplotype. An important role for MHC class II molecules in "determinant selection" is revealed. Amino acids which 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 which bind MHC yet do not crossreact with the autoantigen. Two such peptides compete with the autoantigen for binding to the disease associated class II molecule and inhibit induction of experimental autoimmune encephalomyelitis in H-2u mice. Prospects for peptide mediated therapy are discussed.
Wraith
D C
DC
Division of Immunology, Cambridge University, UK.
Smilek
D E
DE
Mitchell
D J
DJ
Steinman
L
L
McDevitt
H O
HO
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy; D000949:Histocompatibility Antigens Class II; D051379:Mice; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010455:Peptides