Control of T cell antigen reactivity via programmed TCR downregulation

Nat Immunol. 2016 Apr;17(4):379-86. doi: 10.1038/ni.3386. Epub 2016 Feb 22.

Abstract

The T cell antigen receptor (TCR) is unique in that its affinity for ligand is unknown before encounter and can vary by orders of magnitude. How the immune system regulates individual T cells that display very different reactivity to antigen remains unclear. Here we found that activated CD4(+) T cells, at the peak of clonal expansion, persistently downregulated their TCR expression in proportion to the strength of the initial antigen recognition. This programmed response increased the threshold for cytokine production and recall proliferation in a clone-specific manner and ultimately excluded clones with the highest antigen reactivity. Thus, programmed downregulation of TCR expression represents a negative feedback mechanism for constraining T cell effector function with a suitable time delay to thereby allow pathogen control while avoiding excess inflammatory damage.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology
  • Bacterial Proteins / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Down-Regulation*
  • Histocompatibility Antigens Class II / immunology
  • Immunoblotting
  • Listeria monocytogenes
  • Listeriosis / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Mycobacterium tuberculosis
  • Real-Time Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes
  • Th1 Cells / immunology*
  • Transcriptome
  • Tuberculosis, Pulmonary / immunology*

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Histocompatibility Antigens Class II
  • Receptors, Antigen, T-Cell