Influence of a dominant cryptic epitope on autoimmune T cell tolerance

Nat Immunol. 2002 Feb;3(2):175-81. doi: 10.1038/ni756. Epub 2002 Jan 14.


The rules governing which T cells are inactivated during peptide-induced tolerance are unclear. Here we show that MBP(89-101) contains three overlapping but distinct T cell epitopes that are restricted by a single major histocompatibility complex (MHC) class II molecule. The dominant epitope is not processed from MBP and is not relevant to the induction of autoimmunity. Pathogenic T cells recognize two minor epitopes that are processed from MBP but are presented only poorly after exposure to MBP(89-101). Induction of immunological tolerance by MBP(89-101) therefore inactivates T cells that recognize the dominant epitope and disease-relevant T cells escape tolerance. The topology of the three epitopes implicates asparagine endopeptidase as the enzyme that controls recognition of this region of MBP. Our results highlight the need to use peptides that mimic the binding of processed antigen fragments to MHC molecules for successful modulation of disease-relevant T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation
  • Autoimmunity*
  • Clone Cells
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Histocompatibility Antigens Class II
  • Immune Tolerance*
  • Immunodominant Epitopes / immunology*
  • Mice
  • Molecular Sequence Data
  • Myelin Basic Protein / immunology*
  • Peptide Fragments / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology


  • Histocompatibility Antigens Class II
  • Immunodominant Epitopes
  • Myelin Basic Protein
  • Peptide Fragments
  • myelin basic protein 89-101