In situ expansion of T cells that recognize distinct self-antigens sustains autoimmunity in the CNS

Brain. 2016 May;139(Pt 5):1433-46. doi: 10.1093/brain/aww032. Epub 2016 Mar 21.


Polyspecific T cells recognizing multiple distinct self-antigens have been identified in multiple sclerosis and other organ-specific autoimmune diseases, but their pathophysiological relevance remains undetermined. Using a mouse model of multiple sclerosis, we show that autoimmune encephalomyelitis induction is strictly dependent on reactivation of pathogenic T cells by a peptide (35-55) derived from myelin oligodendrocyte glycoprotein (MOG). This disease-inducing response wanes after onset. Strikingly, the progression of disease is driven by the in situ activation and expansion of a minority of MOG35-55-specific T cells that also recognize neurofilament-medium (NF-M)15-35, an intermediate filament protein expressed in neurons. This mobilization of bispecific T cells is critical for disease progression as adoptive transfer of NF-M15-35/MOG35-55 bispecific T cell lines caused full-blown disease in wild-type but not NF-M-deficient recipients. Moreover, specific tolerance through injection of NF-M15-35 peptide at the peak of disease halted experimental autoimmune encephalomyelitis progression. Our findings highlight the importance of polyspecific autoreactive T cells in the aggravation and perpetuation of central nervous system autoimmunity.

Keywords: T cells; TCR; autoimmune disease; central nervous system; experimental autoimmune encephalomyelitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / immunology*
  • Autoimmunity*
  • Cells, Cultured
  • Central Nervous System / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Knockout
  • Myelin-Oligodendrocyte Glycoprotein / immunology*
  • Peptide Fragments / immunology
  • T-Lymphocytes / immunology*


  • Autoantigens
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • myelin oligodendrocyte glycoprotein (35-55)