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

Myasthenia gravis (MG) and its animal model, experimental autoimmune (EA) M G, are caused by T cell-dependent autoantibodies that react with the nicoti nic acetylcholine receptor (AChR) on muscle and interfere with neuromuscula r transmission. Thus, selective inactivation of CD4(+) AChR-specific T help er cells should lower AChR Ab levels and ameliorate disease. In the Lewis r at model of EAMG, alpha chain residues 100-116 of the AChR represent the do minant T cell epitope, which is important in helping Ab responses to this a utoantigen, In the present report, we have applied a new design technique t hat requires no knowledge of Ag receptor sequences on errant T cells in ord er to develop a synthetic peptide vaccine against T cells reactive with the aforementioned T cell epitope, Immunization with the peptide 1) induced po lyclonal and monoclonal Ab, which inhibited AChR 100-116 stimulation of ACh R-sensitized lymphocytes and recognized V beta 15 containing T cell recepto rs on AChR 100-116-specific T cell lines and clones; 2) lowered AChR Ab lev els; 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 applicatio n to human autoimmune diseases.