Editors' ChoiceAutoimmunity

Viral infection crosses up antigen presentation to drive autoimmunity

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Science Translational Medicine  27 Jul 2016:
Vol. 8, Issue 349, pp. 349ec120
DOI: 10.1126/scitranslmed.aah4507

Studies of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), have provided important insights into immune pathology. This model, which is incited by immunization with a portion of the brain protein myelin oligodendrocyte glycoprotein (MOG), is inducible in nonhuman primates, including the common marmoset and the rhesus macaque. Viral infections such as Epstein Barr virus (EBV) are often suspected to trigger autoimmune disease, but molecular mechanisms remain elusive. Using these valuable, translational models, Jagessar and colleagues have identified new pathways by which infection triggers autoimmunity.

The current study connects two previous key findings: B cells are required for EAE development, and the MOG40-48 peptide drives disease. Under normal conditions, B cells tended to destroy the pathologic peptide sequence when processing the MOG protein. The authors tested the hypothesis that viral infection with lymphocryptovirus, an EBV-related virus, alters B cell antigen presentation to enable presentation of the key peptide to pathogenic CD8 T cells responsible for disease progression. The authors discovered that lymphocryptovirus infection of B cells diminished MOG proteolysis and enhanced autophagosome activity, which promotes peptide “cross-presentation.” In this process, antigens, such as MOG, acquired from outside the cell can switch tracks to become presented along with peptides derived from proteins inside the cell, which is the system that activates CD8 T cells. In order to make this switch, infection induced changes in the B cell to protect processed antigen fragments and enhance the CD8 T cell–activating presentation pathway.

Because EBV is a common infection targeting B cells in humans and has been strongly associated with MS and other autoimmune pathologies, this investigation offers a potentially important connection between this infectious process and autoimmune disease. In addition, by determining critical molecular steps that are required, future interventions could limit B cell–mediated antigen presentation and restrict their capacity for cross-presentation of key antigens that promote disease.

S. A. Jagessar et al., Lymphocryptovirus infection of nonhuman primate B cells converts destructive into productive processing of the pathogenic CD8 T cell epitope in myelin oligodendrocyte glycoprotein. J. Immunol. 10.4049/jimmunol.1600124 (2016).[Full Text]

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