EBV Infection Empowers Human B Cells for Autoimmunity
| Autor: | Elena Morandi, Bert A. 't Hart, S. Anwar Jagessar, Bruno Gran |
|---|---|
| Přispěvatelé: | Molecular Neuroscience and Ageing Research (MOLAR) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
EXPRESSION Cathepsin G Multiple Sclerosis Immunology Autoimmunity CD8-Positive T-Lymphocytes Biology medicine.disease_cause LYMPHOCYTES Epitope Myelin oligodendrocyte glycoprotein Mice 03 medical and health sciences Cross-Priming 0302 clinical medicine MYELIN OLIGODENDROCYTE GLYCOPROTEIN Autophagy medicine Animals Humans Immunology and Allergy Cytotoxic T cell EPSTEIN-BARR-VIRUS Cells Cultured B-Lymphocytes Immunodominant Epitopes Experimental autoimmune encephalomyelitis Autophagosomes Citrullination CATHEPSIN-G medicine.disease Virology Epstein–Barr virus BASIC-PROTEIN MODEL CITRULLINATED PROTEINS 030104 developmental biology biology.protein T-CELLS ENCEPHALOMYELITIS Myelin-Oligodendrocyte Glycoprotein 030217 neurology & neurosurgery CD8 |
| Zdroj: | Journal of Immunology, 199(2), 435-448. AMER ASSOC IMMUNOLOGISTS |
| ISSN: | 0022-1767 |
| DOI: | 10.4049/jimmunol.1700178 |
| Popis: | The efficacy of B cell depletion therapy in multiple sclerosis indicates their central pathogenic role in disease pathogenesis. The B lymphotropic EBV is a major risk factor in multiple sclerosis, via as yet unclear mechanisms. We reported in a nonhuman primate experimental autoimmune encephalomyelitis model that an EBV-related lymphocryptovirus enables B cells to protect a proteolysis-sensitive immunodominant myelin oligodendrocyte glycoprotein (MOG) epitope (residues 40–48) against destructive processing. This facilitates its cross-presentation to autoaggressive cytotoxic MHC-E–restricted CD8+CD56+ T cells. The present study extends these observations to intact human B cells and identifies a key role of autophagy. EBV infection upregulated APC-related markers on B cells and activated the cross-presentation machinery. Although human MOG protein was degraded less in EBV-infected than in uninfected B cells, induction of cathepsin G activity by EBV led to total degradation of the immunodominant peptides MOG35–55 and MOG1–20. Inhibition of cathepsin G or citrullination of the arginine residue within an LC3-interacting region motif of immunodominant MOG peptides abrogated their degradation. Internalized MOG colocalized with autophagosomes, which can protect from destructive processing. In conclusion, EBV infection switches MOG processing in B cells from destructive to productive and facilitates cross-presentation of disease-relevant epitopes to CD8+ T cells. |
| Databáze: | OpenAIRE |
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