Bispecificity for myelin and neuronal self-antigens is a common feature of CD4 T cells in C57BL/6 mice

J Immunol. 2014 Oct 1;193(7):3267-77. doi: 10.4049/jimmunol.1400523. Epub 2014 Aug 18.


The recognition of multiple ligands by a single TCR is an intrinsic feature of T cell biology, with important consequences for physiological and pathological processes. Polyspecific T cells targeting distinct self-antigens have been identified in healthy individuals as well as in the context of autoimmunity. We have previously shown that the 2D2 TCR recognizes the myelin oligodendrocyte glycoprotein epitope (MOG)35-55 as well as an epitope within the axonal protein neurofilament medium (NF-M15-35) in H-2(b) mice. In this study, we assess whether this cross-reactivity is a common feature of the MOG35-55-specific T cell response. To this end, we analyzed the CD4 T cell response of MOG35-55-immunized C57BL/6 mice for cross-reactivity with NF-M15-35. Using Ag recall responses, we established that an important proportion of MOG35-55-specific CD4 T cells also responded to NF-M15-35 in all mice tested. To study the clonality of this response, we analyzed 22 MOG35-55-specific T cell hybridomas expressing distinct TCR. Seven hybridomas were found to cross-react with NF-M15-35. Using an alanine scan of NF-M18-30 and an in silico predictive model, we dissected the molecular basis of cross-reactivity between MOG35-55 and NF-M15-35. We established that NF-M F24, R26, and V27 proved important TCR contacts. Strikingly, the identified TCR contacts are conserved within MOG38-50. Our data indicate that due to linear sequence homology, part of the MOG35-55-specific T cell repertoire of all C57BL/6 mice also recognizes NF-M15-35, with potential implications for CNS autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / genetics
  • Autoantigens / immunology*
  • Autoimmune Diseases of the Nervous System / genetics
  • Autoimmune Diseases of the Nervous System / immunology
  • Autoimmune Diseases of the Nervous System / pathology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • Cross Reactions / genetics
  • Cross Reactions / immunology
  • Mice
  • Mice, Knockout
  • Myelin Sheath / genetics
  • Myelin Sheath / immunology*
  • Myelin-Oligodendrocyte Glycoprotein / genetics
  • Myelin-Oligodendrocyte Glycoprotein / immunology*
  • Neurofilament Proteins / genetics
  • Neurofilament Proteins / immunology*
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Receptors, Antigen / genetics
  • Receptors, Antigen / immunology*


  • Autoantigens
  • Myelin-Oligodendrocyte Glycoprotein
  • Neurofilament Proteins
  • Peptide Fragments
  • Receptors, Antigen
  • myelin oligodendrocyte glycoprotein (35-55)
  • neurofilament protein M