title: Neonatal tolerance to an immunodominant T cell reactivity does not confer resistance to EAMG induction in Lewis rats.
abstract: 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.
authors.affiliation: Department of Microbiology, University of Texas Health Science Center, San Antonio 78284, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: Zoda
authors.forename: K
authors.initials: K
authors.lastname: Brandon
authors.forename: K A
authors.initials: KA
authors.lastname: Krolick
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000917:Antibody Formation; D000939:Epitopes; D005260:Female; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000939:Epitopes; D010446:Peptide Fragments; D011950:Receptors, Cholinergic