HLA-DQ6 transgenic mice resistance to experimental autoimmune myasthenia gravis is linked to reduced acetylcholine receptor-specific IFN-gamma, IL-2 and IL-10 production

To comprehend the reduced susceptibility of HLA-DQ6 transgenic mice in comp arison with HLA-DQ8 mice, to experimental autoimmune myasthenia gravis. (EA MG), we immunized them with acetylcholine receptor (AChR) and examined in v itro, the proliferative and cytokine responses to AChR. When immunized with AChR and examined for AChR-specific lymphocyte responses to AChR, EAMG-res istant DQ6 mice exhibited significantly reduced in vitro lymphoproliferativ e and cytokine responses to AChR, compared to DQ8 mice. The differences in susceptibility were not linked to a difference in peptide recognition by AC hR-specific lymphocytes. AChR T cell epitope mapping showed that both DQ6 a nd DQ8 responded to the same epitopes, although to varying degrees. Resista nce of DQ6 transgenic mice to EAMG was linked to a dramatic suppression of AChR-specific IFN-gamma, IL-2 and IL-10 productions by AChR-primed lymph no de cells. (C) 2001 Academic Press.