Nitration of MOG diminishes its encephalitogenicity depending on MHC haplotype

J Neuroimmunol. 2017 Feb 15:303:1-12. doi: 10.1016/j.jneuroim.2016.11.008. Epub 2016 Nov 26.


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 H2b C57BL/6 mice. Furthermore, nitrated MOG displays inferior antigen-specific proliferation of 2D2 splenocytes in vitro. Conversely, H2q 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 MOG35-55/H2-IAb 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-IAb to efficiently present the altered peptide ligand of MOG35-55 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.

Keywords: 3-Nitrotyrosine; Antigen presentation; Autoimmunity; Epitope spreading; Experimental autoimmune encephalomyelitis; Major histocompatibility complex; Myelin oligodendrocyte glycoprotein; Oxidative stress; Post-translational modification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Female
  • Haplotypes*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Myelin-Oligodendrocyte Glycoprotein / genetics
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Myelin-Oligodendrocyte Glycoprotein / metabolism*
  • Nitrates / immunology
  • Nitrates / metabolism*
  • Protein Binding / physiology
  • Protein Structure, Secondary
  • Protein Structure, Tertiary


  • Myelin-Oligodendrocyte Glycoprotein
  • Nitrates