title: A polyalanine peptide with only five native myelin basic protein residues induces autoimmune encephalomyelitis.
abstract: The minimum structural requirements for peptide interactions with major histocompatibility complex (MHC) class II molecules and with T cell receptors (TCRs) were examined. In this report we show that substituting alanines at all but five amino acids in the myelin basic protein (MBP) peptide Ac1-11 does not alter its ability to bind A alpha uA beta u (MHC class II molecules), to stimulate specific T cells and, surprisingly, to induce experimental autoimmune encephalomyelitis (EAE) in (PL/J x SJL/J)F1 mice. Most other amino acid side chains in the Ac1-11 peptide are essentially irrelevant for T cell stimulation and for disease induction. Further analysis revealed that binding to A alpha uA beta u occurred with a peptide that consists mainly of alanines and only three of the original residues of Ac1-11. Moreover, when used as a coimmunogen with MBP Ac1-11, this peptide inhibited EAE. The finding that a specific in vivo response can be generated by a peptide containing only five native residues provides evidence that disease-inducing TCRs recognize only a very short sequence of the MHC-bound peptide.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305.
authors.forename: A M
authors.initials: AM
authors.lastname: Gautam
authors.forename: C I
authors.initials: CI
authors.lastname: Pearson
authors.forename: D E
authors.initials: DE
authors.lastname: Smilek
authors.forename: L
authors.initials: L
authors.lastname: Steinman
authors.forename: H O
authors.initials: HO
authors.lastname: McDevitt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D004679:Encephalomyelitis / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; C019529:polyalanine