Molecular mimics can induce a nonautoaggressive repertoire that preempts induction of autoimmunity

Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2550-5. doi: 10.1073/pnas.0914508107. Epub 2010 Jan 20.


To determine the role that competition plays in a molecular mimic's capacity to induce autoimmunity, we studied the ability of naïve encephalitogenic T cells to expand in response to agonist altered peptide ligands (APLs), some capable of stimulating both self-directed and exclusively APL-specific T cells. Our results show that although the APLs capable of stimulating exclusively APL-specific T cells are able to expand encephalitogenic T cells in vitro, the encephalitogenic repertoire is effectively outcompeted in vivo when the APL is used as the priming immunogen. Competition as a mechanism was supported by: (i) the demonstration of a population of exclusively APL-specific T cells, (ii) an experiment in which an encephalitogenic T cell population was successfully outcompeted by adoptively transferred naïve T cells, and (iii) demonstrating that the elimination of competing T cells bestowed an APL with the ability to expand naïve encephalitogenic T cells in vivo. In total, these experiments support the existence of a reasonably broad T cell repertoire responsive to a molecular mimic (e.g., a microbial agent), of which the exclusively mimic-specific component tends to focus the immune response on the invading pathogen, whereas the rare cross-reactive, potentially autoreactive T cells are often preempted from becoming involved.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoimmunity / immunology*
  • Cell Proliferation
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Flow Cytometry
  • Immunization
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Mice
  • Oligopeptides / immunology
  • Receptors, Antigen, T-Cell / immunology*
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*


  • Oligopeptides
  • Receptors, Antigen, T-Cell