T cell division and death are segregated by mutation of TCRbeta chain constant domains

Immunity. 2004 Oct;21(4):515-26. doi: 10.1016/j.immuni.2004.08.014.


We have studied the role of the T cell receptor (TCR) beta chain transmembrane and cytoplasmic domains (betaTM/Cyto) in T cell signaling. Upon antigen stimulation, T lymphocytes expressing a TCR with mutant and betaTM and Cyto domains accumulate in large numbers and are specifically defective in undergoing activation-induced cell death (AICD). The mutant TCR poorly recruits the protein adaptor Carma-1 and is subsequently impaired in activating NF-kappaB. This signaling defect leads to a reduced expression of Fas ligand (FasL) and to a reduction in AICD. These beta chain domains are involved in discriminating cell division and apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Apoptosis / physiology*
  • Blotting, Western
  • Cell Division / immunology*
  • Fas Ligand Protein
  • Flow Cytometry
  • Interleukin-2 / metabolism
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Mutation
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Protein Structure, Tertiary / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Interleukin-2
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD6 antigen
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Interleukin-2
  • Membrane Glycoproteins
  • NF-kappa B
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Interleukin-2