A polyalanine peptide with only five native myelin basic protein residues induces autoimmune encephalomyelitis

doi:10.1084/jem.176.2.605

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A polyalanine peptide with only five native myelin basic protein residues induces autoimmune encephalomyelitis

AM Gautam, CI Pearson, DE Smilek, L Steinman and HO McDevitt
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305.

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.
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