An epitope from Acanthamoeba castellanii induces clinical signs of autoimmune encephalomyelitis in SJL mice by molecular mimicry. (93.25)

Abstract Autoimmune responses to myelin antigens have been implicated in the pathogenesis of multiple sclerosis (MS), but the mechanisms by which the disease is initiated are unknown. Exposure to environmental microbes has been suspected to initiate the disease by generating autoreactive cells as a result of the release of new antigens, bystander activation and molecular mimicry. We have identified an epitope (aa, 83-95) from Acanthamoeba castellanii (ACA) and it induces clinical signs of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice reminiscent of the disease induced with myelin proteolipid protein (PLP) 139-151 regardless of gender. By using major histocompatibility complex II / IAs tetramers, we demonstrate that both ACA 83-95 and PLP 139-151 generate antigen-specific cross-reactive CD4 T cells and the T cells secrete identical patterns of T helper (Th) 1 and Th 17 cytokines. However, by contrasting the differences in TCR Vβ usage, it was revealed that the T cells from mice immunized with ACA 83-95 showed a higher proportion of Vβ2+ T cells with a corresponding decrease in Vβ17a+ cells and the reverse pattern was observed in mice immunized with PLP 139-151. These results may provide insights into the pathogenesis of multiple sclerosis and ACA-induced granulomatous encephalitis.