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Related Experiment Videos

T-cell-receptor isoforms.

L K Clayton1, A Lerner, A C Diener

  • 1Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115.

International Journal of Cancer. Supplement = Journal International Du Cancer. Supplement
|January 1, 1992
PubMed
Summary

The T-cell receptor (TCR) zeta-eta and zeta-zeta forms signal similarly for T-cell activation and death. Human T cells do not express CD3 eta protein, despite mouse expression.

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Area of Science:

  • Immunology
  • Molecular Biology

Background:

  • Early studies suggested a link between CD3 zeta-eta heterodimers and T-cell signaling, including phosphatidyl-inositol (PI) turnover and activation-induced cell death.
  • The cloning of CD3 eta enabled direct analysis of T-cell receptor (TCR) signaling complexes containing CD3 zeta-zeta, CD3 zeta-eta, and CD3 eta-eta.

Purpose of the Study:

  • To investigate the signal transduction properties of different T-cell receptor (TCR) complexes.
  • To determine the expression and function of CD3 eta in T-cell signaling and development.
  • To compare CD3 eta expression and function in mice and humans.

Main Methods:

  • Analysis of signal transduction in T-cell hybridomas expressing various TCR complexes.
  • Immunohistochemical staining of thymic sections using anti-CD3 eta monoclonal antibodies.
  • Generation and analysis of CD3 eta transgenic mice.
  • Genomic analysis of the human CD3 zeta-eta locus.

Main Results:

  • All TCR forms (zeta-zeta, zeta-eta, eta-eta) effectively transduce signals for PI turnover, calcium mobilization, IL-2 production, and cell-cycle arrest.
  • CD3 zeta and CD3 eta share a promoter, leading to coordinated expression, making restricted CD3 eta expression unlikely in thymocytes.
  • No detectable CD3 eta protein was found in adult mouse thymus sections, suggesting low constitutive expression.
  • CD3 eta is readily detected in thymocytes of CD3 eta transgenic mice, but its overexpression does not increase negative selection.
  • No CD3 eta message was detected in human thymus or T cells, and despite genomic homology, the human CD3 eta protein sequence is not homologous to the mouse counterpart.

Conclusions:

  • TCR complexes containing CD3 zeta-zeta, CD3 zeta-eta, and CD3 eta-eta exhibit similar signaling capabilities.
  • CD3 eta expression is unlikely to be restricted in mouse thymocytes due to shared promoter regulation.
  • Overexpression of CD3 eta in mice does not significantly impact negative selection.
  • A functional CD3 eta protein is absent in human T cells, despite sequence homology in the genomic locus.

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