Immunogenicity of Torpedo acetylcholine receptor in the context of different rat MHC class II haplotypes and non-MHC genomes

The nicotinic acetylcholine receptor (nAChR) is the autoantigen in seropositive myasthenia gravis (MG), a T-cell-dependent B-cell-mediated autoimmune disease. The nAChR is a pentameric transmembrane receptor comprising alphaalphabetagammadelta chains. During early postnatal development the nAChR gamma chain is replaced by the nAChR epsilon chain. We tested the myasthenogenicity in experimental autoimmune myasthenia gravis (EAMG) of the native nAChR derived from the electric ray Torpedo californica (T-nAChR) in various inbred and MHC -congenic rat strains. Differences in the disease course emerged dependent on the MHC haplotype and non-MHC genes. Interestingly, no tested rat strain was completely resistant to EAMG, but there were strong differences in disease severity mainly depending on the MHC haplotype. In the LEW non-MHC genome, the B-cell response and the severity of EAMG were dependent on the expressed MHC haplotype. This study underscores the influence of genetic factors on disease severity, disease course and on the degree of the emerging antibody responses in EAMG.