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 alpha alpha beta gamma delta 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.
Gaertner
Susanne
S
Experimental Neuroimmunology, Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler Strasse 3, 72076 Tuebingen, Germany.
de Graaf
Katrien L
KL
Olsson
Tomas
T
Weissert
Robert
R
D000818:Animals; D020296:Animals, Congenic; D005260:Female; D005802:Genes, MHC Class II; D016678:Genome; D006239:Haplotypes; D006801:Humans; D007114:Immunization; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000276:immunology*; D014101:Torpedo
D011978:Receptors, Nicotinic