Gender differences in CNS autoimmunity induced by mimicry epitope for PLP 139–151 in SJL mice

Development of multiple sclerosis (MS) is more prevalent in females than in males, but the underlying mechanisms are not clear. Microbial infections have been suspected as triggers of MS and it is not known whether gender differences in reactivity to environmental antigens contribute to the disease pathogenesis. We demonstrated that ACA 83–95, a mimicry epitope from Acanthamoeba castellanii for proteolipid protein (PLP) 139–151, induces clinical signs of encephalomyelitis in both male and female SJL mice. Conversely ACA 83–95-induced effector cells from males fail to induce disease in female mice. Although we found no gender differences in the frequencies of antigen-specific cells including cytokine production, PLP-specific cells induced with ACA 83–95 differed in T cell receptor vβ usage from those induced with PLP 139–151. The data suggest that cross-reactive T cell expansion occurs similarly in both males and females, but their disease-inducing ability is influenced by gender.