Oral administration of an immunodominant T-cell epitope downregulates Th1/Th2 cytokines and prevents experimental myasthenia gravis

J Clin Invest. 1999 Nov;104(9):1287-95. doi: 10.1172/JCI7121.


The mucosal administration of the native antigen or peptide fragments corresponding to immunodominant regions is effective in preventing or treating several T cell-dependent models of autoimmune disease. No data are yet available on oral tolerance with immunodominant T-cell peptides in experimental autoimmune myasthenia gravis (EAMG), an animal model of B cell-dependent disease. We report that oral administration of the T-cell epitope alpha146-162 of the Torpedo californica acetylcholine receptor (TAChR) alpha-subunit suppressed T-cell responses to AChR and ameliorated the disease in C57Bl/6 (B6) mice. Protection from EAMG was associated with reduced serum Ab's to mouse AChR and reduced AChR loss in muscle. The effect of Talpha146-162 feeding was specific; treatment with a control peptide did not affect EAMG manifestations. The protective effect induced by peptide Talpha146-162 was mediated by reduced production of IFN-gamma, IL-2, and IL-10 by TAChR-reactive cells, suggesting T-cell anergy. TGF-beta-secreting Th3 cells did not seem to be involved in tolerance induction. We therefore demonstrate that feeding a single immunodominant epitope can prevent an Ab-mediated experimental model of autoimmune disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Cytokines / metabolism*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Epitopes, T-Lymphocyte / administration & dosage*
  • Epitopes, T-Lymphocyte / pharmacology
  • Mice
  • Myasthenia Gravis / immunology
  • Myasthenia Gravis / prevention & control*
  • Peptides / pharmacology
  • Receptors, Cholinergic / immunology
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th2 Cells / drug effects*
  • Th2 Cells / immunology
  • Transcription, Genetic / drug effects
  • Transforming Growth Factor beta / genetics


  • Cytokines
  • Epitopes, T-Lymphocyte
  • Peptides
  • Receptors, Cholinergic
  • Transforming Growth Factor beta