A peptide vaccine that prevents experimental autoimmune myasthenia gravis by specifically blocking T cell help

Academic Article


  • Myasthenia gravis (MG) and its animal model, experimental autoimmune (EA) MG, are caused by T cell-dependent autoantibodies that react with the nicotinic acetylcholine receptor (AChR) on muscle and interfere with neuromuscular transmission. Thus, selective inactivation of CD4+ AChR- specific T helper cells should lower AChR Ab levels and ameliorate disease. In the Lewis rat model of EAMG, α chain residues 100-116 of the AChR represent the dominant T cell epitope, which is important in helping Ab responses to this autoantigen. In the present report, we have applied a new design technique that requires no knowledge of Ag receptor sequences on errant T cells in order to develop a synthetic peptide vaccine against T cells reactive with the aforementioned T cell epitope. Immunization with the peptide 1) induced polyclonal and monoclonal Ab, which inhibited AChR 100-116 stimulation of AChR-sensitized lymphocytes and recognized Vβ15 containing T cell receptors on AChR 100-116-specific T cell lines and clones; 2) lowered AChR Ab levels; 3) reduced the loss of muscle AChR; and 4) lessened the incidence and severity of EAMG. These findings suggest a new strategy for the functional abrogation of epitope-specific T cells that could have potential application to human autoimmune diseases.
  • Published In

  • The FASEB Journal  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 20554934
  • Author List

  • Araga S; Xu L; Nakashima K; Villain M; Blalock JE
  • Start Page

  • 185
  • End Page

  • 196
  • Volume

  • 14
  • Issue

  • 1