Synthetic peptides corresponding to selected sequences from the nicotinic acetylcholine receptor (AChR) were employed to identify possible antigenic determinants within the receptor which can modulate the anti-AChR response and experimental autoimmune myasthenia gravis (EAMG). Immunization of rabbits with peptides Tα73-89 Tα351-368, Tδ354-367 and Hα351-368, prior to AChR inoculation, affected the course of EAMG in six out of eight rabbits. These six protected rabbits survived three inoculations of AChR and survived for at least five months after the third injection with AChR, whereas control rabbits died following one or two injections of AChR. The survival of peptide-preimmunized rabbits injected with AChR seemed to correlate with the antibody specificities in immunoblots. Following AChR inoculation there was a shift in reactivity, from a subunit-restricted response, to reactivity with all subunits of the receptor. This shift was delayed in protected rabbits. This may indicate that the reactivity with the entire Torpedo receptor molecule represents a loss of tolerance to AChR which culminates in the autoimmune disease, EAMG.
Bibliographical noteFunding Information:
This work was supported by grants from the Association Franqaise Contre les Myopathies (AFM), the Los Angeles Chapter of the Myasthenia Gravis Foundation, the Muscular Dystrophy Association of America, the United States-Israel Binational Science Foundation (BSF) and the Schilling Foundation.
- Acetylcholine receptor
- Myasthenia gravis
- Synthetic peptide