NEONATAL TOLERANCE TO AN IMMUNODOMINANT T-CELL REACTIVITY DOES NOT CONFER RESISTANCE TO EAMG INDUCTION IN LEWIS RATS

The overall goal of this study was to determine, during induction of e xperimental autoimmune myasthenia gravis (EAMG) in Lewis rats, the rel ative importance of acetylcholine receptor (AChR)-reactive helper T ce lls associated with one particular immunodominant fine specificity. Th us, experiments presented below were designed to evaluate the immunopa thological role played by helper T cells with reactivity against the A ChR alpha subunit region associated with amino acid residues 100-116 ( i.e., alpha 100-116); in particular, the relationship between T cell r eactivity 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 100-11 6 and subsequently evaluated for anti-AChR antibody production and res ulting neuromuscular dysfunction. Results indicated that although T ce ll reactivity against the alpha 100-116 peptide could be effectively r emoved from the Lewis T cell repertoire, tolerized Lewis rats immunize d with AChR could undergo an active anti-AChR antibody response that p roduced symptoms of EAMG. Thus, other AChR T cell reactivities appeare d capable of providing adequate help to B cells leading to production of anti-AChR antibodies with pathogenic potential.