The overall goal of this study was to determine, during induction of experimental autoimmune myasthenia gravis (EAMG) in Lewis rats, the relative importance of acetylcholine receptor (AChR)-reactive helper T cells associated with one particular immunodominant fine specificity. Thus, experiments presented below were designed to evaluate the immunopathological role played by helper T cells with reactivity against the AChR alpha subunit region associated with amino acid residues 100-116 (i.e., alpha 100-116); in particular, the relationship between T cell reactivity with this specificity and disease induction was assessed. In order to examine the importance of this T cell reactivity, Lewis rat neonates were made T cell tolerant to a synthetic peptide alpha 100-116 and subsequently evaluated for anti-AChR antibody production and resulting neuromuscular dysfunction. Results indicated that although T cell reactivity against the alpha 100-116 peptide could be effectively removed from the Lewis T cell repertoire, tolerized Lewis rats immunized with AChR could undergo an active anti-AChR antibody response that produced symptoms of EAMG. Thus, other AChR T cell reactivities appeared capable of providing adequate help to B cells leading to production of anti-AChR antibodies with pathogenic potential.