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Nitration of MOG diminishes its encephalitogenicity depending on MHC haplotype
Karolinska Univ Hosp, Ctr Mol Med, Karolinska Inst, Dept Clin Neurosci Appl Immunol & Immunotherapy, S-17176 Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
Karolinska Univ Hosp, Ctr Mol Med, Karolinska Inst, Dept Clin Neurosci Appl Immunol & Immunotherapy, S-17176 Stockholm, Sweden..
Karolinska Univ Hosp, Karolinska Inst, Dept Infect Dis, Dept Med Solna,Sci Life Lab, SE-17176 Stockholm, Sweden..
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2017 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 303, 1-12 p.Article in journal (Refereed) Published
Abstract [en]

Post-translational modifications of autoantigens are hypothesized to affect their immunogenicity. We here report that nitration of tyrosine 40 in Myelin Oligodendrocyte Glycoprotein (MOG) abrogates its encephalitogenicity both at protein and peptide levels in the experimental autoimmune encephalomyelitis (EAE) model in H2(b) C57BL/6 mice. Furthermore, nitrated MOG displays inferior antigen-specific proliferation of 2D2 splenocytes in vitro. Conversely, H2(q) DBA1 mice remain fully susceptible to EAE induction using nitrated MOG as the dominant epitope of H2q mice is unaltered. Molecular modeling analysis of the MOG(35-55)/H2-lA(b) complex and bioinformatics peptide binding predictions indicate that the lack of T cell reactivity towards nitrated MOG can be attributed to the inability of murine H2-IA(b) to efficiently present the altered peptide ligand of MOG(35-55) because the nitrated tyrosine 40 cannot be accommodated in the p1 anchor pocket. In conclusion we demonstrate nitration as a relevant determinant affecting T cell recognition of carrier antigen depending on MHC haplotype. Our data have implications for understanding the role of post-translationally modified antigen in autoimmunity. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.

Place, publisher, year, edition, pages
2017. Vol. 303, 1-12 p.
Keyword [en]
3-Nitrotyrosine, Post-translational modification, Myelin oligodendrocyte glycoprotein, Experimental autoimmune encephalomyelitis, Antigen presentation, Major histocompatibility complex, Autoimmunity, Oxidative stress, Epitope spreading
National Category
Neurosciences Immunology
Identifiers
URN: urn:nbn:se:uu:diva-317945DOI: 10.1016/j.jneuroim.2016.11.008ISI: 000393629100001PubMedID: 28011088OAI: oai:DiVA.org:uu-317945DiVA: diva2:1086340
Available from: 2017-04-01 Created: 2017-04-01 Last updated: 2017-04-01Bibliographically approved

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