Processing of native or citrullinated myelin oligodendrocyte glycoprotein peptides in B cells is affected by EBV infection: implications for multiple sclerosis (APP5P.118)

Abstract

Abstract Multiple Sclerosis is a neurodegenerative disease with an immune-mediated pathogenesis in which Epstein Barr Virus (EBV) is a risk factor. EBV infects human B cells, in which it becomes latent. Our hypothesis is that infection renders B cells potent APC for autoreactive T cells, through influences on intracellular proteolysis and post-translational modifications of self antigens. The aim of this study is to assess the effect of EBV infection of B cells on processing of myelin oligodendrocyte glycoprotein (MOG). We investigated the processing of recombinant extracellular MOG and of the immunodominant peptides MOG1-20, MOG35-55 and through SDS PAGE gel analysis in the presence or absence of Cathepsin inhibitors. We also studied the effect of MOG35-55 citrullination in position 41 and 46. In addition, we determined the proteolytic activity of Cathepsin G and H by activity assay. We found that EBV infection increases the activity of Cathepsin G and H, leading to increased degradation of MOG35-55 by B cells. However, infection also rescues rhMOG from total degradation. By contrast, inhibition of Cathepsin G or citrullination of Arg 46 abrogated the degradation of MOG35-55. These results indicate that citrullination of an immunodominant peptide of MOG protects it from destructive processing in EBV infected B cells. This could facilitate presentation of a disease-relevant myelin autoantigen that may be involved in disease induction and progression.