Tolerance is established in polyclonal CD4(+) T cells by distinct mechanisms, according to self-peptide expression patterns

Nat Immunol. 2016 Feb;17(2):187-95. doi: 10.1038/ni.3327. Epub 2016 Jan 4.


Studies of repertoires of mouse monoclonal CD4(+) T cells have revealed several mechanisms of self-tolerance; however, which mechanisms operate in normal repertoires is unclear. Here we studied polyclonal CD4(+) T cells specific for green fluorescent protein expressed in various organs, which allowed us to determine the effects of specific expression patterns on the same epitope-specific T cells. Peptides presented uniformly by thymic antigen-presenting cells were tolerated by clonal deletion, whereas peptides excluded from the thymus were ignored. Peptides with limited thymic expression induced partial clonal deletion and impaired effector T cell potential but enhanced regulatory T cell potential. These mechanisms were also active for T cell populations specific for endogenously expressed self antigens. Thus, the immunotolerance of polyclonal CD4(+) T cells was maintained by distinct mechanisms, according to self-peptide expression patterns.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Autoantigens / chemistry
  • Autoantigens / genetics
  • Autoantigens / immunology
  • Autoimmunity
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Clonal Deletion / genetics
  • Clonal Deletion / immunology
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Gene Expression*
  • Genes, Reporter
  • Immune Tolerance*
  • Mice
  • Mice, Transgenic
  • Peptides / chemistry
  • Peptides / genetics*
  • Peptides / immunology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / immunology
  • Thymus Gland / metabolism


  • Autoantigens
  • Epitopes, T-Lymphocyte
  • Peptides