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 language | English |
|---|---|
| Pages (from-to) | 2697-2703 |
| Number of pages | 7 |
| Journal | Journal of Immunology |
| Volume | 172 |
| Issue number | 4 |
| Publication status | Published - Feb 15 2004 |
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ASJC Scopus subject areas
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Breakdown of Tolerance to A Self-Peptide of Acetylcholine Receptor α-Subunit Induces Experimental Myasthenia Gravis in Rats
AU - Baggi, Fulvio
AU - Annoni, Andrea
AU - Ubiali, Federica
AU - Milani, Monica
AU - Longhi, Renato
AU - Scaioli, Widmer
AU - Cornelio, Ferdinando
AU - Mantegazza, Renato
AU - Antozzi, Carlo
PY - 2004/2/15
Y1 - 2004/2/15
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0842300349&partnerID=8YFLogxK
M3 - Article
C2 - 14764745
AN - SCOPUS:0842300349
VL - 172
SP - 2697
EP - 2703
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -