Fine-tuning T cell receptor signaling to control T cell development

Trends Immunol. 2014 Jul;35(7):311-8. doi: 10.1016/j.it.2014.05.003. Epub 2014 Jun 17.

Abstract

T cell development from immature CD4(+)CD8(+) double-positive (DP) thymocytes to the mature CD4 or CD8 single-positive (SP) stage requires proper T cell receptor (TCR) signaling. The current working model of thymocyte development is that the strength of the TCR-mediated signal - from little-or-none, through intermediate, to strong - received by the immature cells determines whether they will undergo death by neglect, positive selection, or negative selection, respectively. In recent years, several developmentally regulated, stage-specifically expressed proteins and miRNAs have been found that act like fine-tuners for signal transduction and propagation downstream of the TCR. This allows them to govern thymocyte positive selection. Here, we summarize recent findings on these molecules and suggest new concepts of TCR positive-selection signaling.

Keywords: T cell development; Tespa1; Themis; miR-181; signaling; thymocyte; voltage-gated sodium channel.

Publication types

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

MeSH terms

  • Animals
  • Calcium Signaling
  • Cell Differentiation
  • Clonal Selection, Antigen-Mediated
  • Fetal Proteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • MicroRNAs / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
  • Receptor Cross-Talk
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / immunology*
  • Thymocytes / immunology*

Substances

  • Fetal Proteins
  • Intracellular Signaling Peptides and Proteins
  • MicroRNAs
  • Receptors, Antigen, T-Cell
  • thymocyte-expressed molecule involved in selection, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6