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 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.
Zoda
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Department of Microbiology, University of Texas Health Science Center, San Antonio 78284, USA.
Brandon
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Krolick
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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*
D000939:Epitopes; D010446:Peptide Fragments; D011950:Receptors, Cholinergic