title: T cell responses in EAMG-susceptible and non-susceptible mouse strains after immunization with overlapping peptides encompassing the extracellular part of Torpedo californica acetylcholine receptor alpha chain. Implication to role in myasthenia gravis of autoimmune T-cell responses against receptor degradation products.
abstract: To study the role in myasthenia gravis (MG) of peptides resulting from acetylcholine receptor (AChR) degradation, we examined the ability of AChR peptides to induce T cell responses that are capable of cross-reacting with intact AChR. The studies were carried out in an experimental autoimmune MG (EAMG)-susceptible mouse strain [C57BL/6 (B6)] as well as in two non-susceptible strains [B6.C-H-2bm12 (bm12) and C3H/He]. A set of overlapping peptides encompassing the extracellular part (residues 1-210) of the alpha-chain of Torpedo californica (t) AChR were used, individually or in equimolar mixtures, as immunogens. In B6, immunization with peptides alpha45-60, alpha111-126, alpha146-162 and alpha182-198 gave T cells that responded in vitro to the correlate immunizing peptide. Only the T cells against the latter three peptides cross-reacted with tAChR. Peptide alpha146-162 exhibited the highest in vitro reaction with the immunizing peptide and cross-reaction with tAChR. T cells obtained by immunization of B6 with an equimolar mixture of the peptides responded in vitro to peptides alpha111-126, alpha146-162 and alpha182-198 and cross-reacted very strongly with tAChR. In bm12 and C3H/He, a number of peptides evoked, when used individually as immunogens, strong or moderate T cell responses that recognized in vitro the correlate immunizing peptide but cross-reacted poorly with tAChR. Immunization with the mixture of the peptides gave T cells that recognized several peptides in each strain butdid not cross-react with alpha146-162 or tAChR. The results indicate that the ability to recognize alpha146-162 or AChR by T cells against peptides resulting from receptor degradation can account for the susceptibility to, and aggravation of, MG in B6.
authors.affiliation: Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: M
authors.initials: M
authors.lastname: Oshima
authors.forename: T
authors.initials: T
authors.lastname: Yokoi
authors.forename: P
authors.initials: P
authors.lastname: Deitiker
authors.forename: M Z
authors.initials: MZ
authors.lastname: Atassi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D007114:Immunization; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011950:Receptors, Cholinergic / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014101:Torpedo / Q000276:immunology
chemical_list: D001323:Autoantibodies; D010446:Peptide Fragments; D011950:Receptors, Cholinergic