Breakdown of Tolerance to A Self-Peptide of Acetylcholine Receptor α-Subunit Induces Experimental Myasthenia Gravis in Rats

Fulvio Baggi, Andrea Annoni, Federica Ubiali, Monica Milani, Renato Longhi, Widmer Scaioli, Ferdinando Cornelio, Renato Mantegazza, Carlo Antozzi

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Abstract

Experimental autoimmune myasthenia gravis (EAMG), a model for human myasthenia (MG), is routinely induced in susceptible rat strains by a single immunization with Torpedo acetylcholine receptor (TAChR). TAChR immunization induces anti-AChR Abs that cross-react with self AChR, activate the complement cascade, and promote degradation of the postsynaptic membrane of the neuromuscular junction. In parallel, TAChR-specific T cells are induced, and their specific immunodominant epitope has been mapped to the sequence 97-116 of the AChR α subunit. A proliferative T cell response against the corresponding rat sequence (R97-116) was also found in TAChR-immunized rats. To test whether the rat (self) sequence can be pathogenic, we immunized Lewis rats with R97-116 or T97-116 peptides and evaluated clinical, neurophysiological, and immunological parameters. Clinical signs of the disease were noted only in R97-116-immunized animals and were confirmed by electrophysiological signs of impaired neuromuscular transmission. All animals produced Abs against the immunizing peptide, but anti-rat AChR Abs were observed only in animals immunized with the rat peptide. These findings suggested that EAMG in rats can be induced by a single peptide of the self AChR, that this sequence is recognized by T cells and Abs, and that breakdown of tolerance to a self epitope might be an initiating event in the pathogenesis of rat EAMG and MG.

Original languageEnglish
Pages (from-to)2697-2703
Number of pages7
JournalJournal of Immunology
Volume172
Issue number4
Publication statusPublished - Feb 15 2004

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Autoimmune Experimental Myasthenia Gravis
Peptide Receptors
Cholinergic Receptors
R 97
Torpedo
Peptides
T-Lymphocytes
Immunization
Immunodominant Epitopes
Neuromuscular Junction
Epitopes

ASJC Scopus subject areas

  • Immunology

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Breakdown of Tolerance to A Self-Peptide of Acetylcholine Receptor α-Subunit Induces Experimental Myasthenia Gravis in Rats. / Baggi, Fulvio; Annoni, Andrea; Ubiali, Federica; Milani, Monica; Longhi, Renato; Scaioli, Widmer; Cornelio, Ferdinando; Mantegazza, Renato; Antozzi, Carlo.

In: Journal of Immunology, Vol. 172, No. 4, 15.02.2004, p. 2697-2703.

Research output: Contribution to journalArticle

Baggi, Fulvio ; Annoni, Andrea ; Ubiali, Federica ; Milani, Monica ; Longhi, Renato ; Scaioli, Widmer ; Cornelio, Ferdinando ; Mantegazza, Renato ; Antozzi, Carlo. / Breakdown of Tolerance to A Self-Peptide of Acetylcholine Receptor α-Subunit Induces Experimental Myasthenia Gravis in Rats. In: Journal of Immunology. 2004 ; Vol. 172, No. 4. pp. 2697-2703.
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