TOX: An HMG Box Protein Implicated in the Regulation of Thymocyte Selection

Nat Immunol. 2002 Mar;3(3):272-80. doi: 10.1038/ni767. Epub 2002 Feb 19.

Abstract

In the thymus, pre-T cell receptor (pre-TCR)--mediated signaling and then TCR-mediated signaling initiate changes in gene expression that result in the maturation of CD4 and CD8 lineage T cells from common precursors. Using gene chip technology, we isolated a murine gene, designated Tox, that encodes a member of the HMG (high-mobility group) box family of DNA-binding proteins. TOX expression is up-regulated by both pre-TCR and TCR activation of immature thymocytes but not by TCR activation of mature naïve T cells. Transgenic mice that express TOX show expanded CD8+ and reduced CD4+ single positive thymocyte subpopulations. We present evidence here that this phenotype results from a perturbation in lineage commitment due to reduced sensitivity to TCR-mediated signaling. This molecular marker of thymic selection events may therefore play a role in establishing the activation threshold of developing T cells and patterning changes in gene expression.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • CD5 Antigens / analysis
  • Cell Differentiation
  • Cell Lineage
  • Gene Expression Regulation, Developmental
  • HMGB Proteins / genetics
  • HMGB Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell / physiology
  • T-Lymphocytes / physiology*
  • Up-Regulation

Substances

  • CD5 Antigens
  • HMGB Proteins
  • Receptors, Antigen, T-Cell

Associated data

  • GENBANK/AA184909
  • GENBANK/AB018351
  • GENBANK/AB018651
  • GENBANK/AF472514