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Transcription of T cell antigen receptor genes is induced by protein kinase C activation

T Lindsten1, C H June, C B Thompson

  • 1Howard Hughes Medical Institute, Ann Arbor, MI 48109.

Journal of Immunology (Baltimore, Md. : 1950)
|September 1, 1988
PubMed

Insights

Protein kinase C activation in Jurkat T cells modulates T cell receptor (TCR)-alpha/beta expression. This leads to increased TCR-alpha and -beta mRNA levels via transcriptional activation, alongside decreased c-myc proto-oncogene expression.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • T cell receptor (TCR) alpha and beta gene expression is crucial for T cell function.
  • Jurkat T cell lines are a common model for studying T cell activation and signaling.

Purpose of the Study:

  • To investigate the regulation of TCR-alpha and -beta gene expression in Jurkat T cells.
  • To identify signaling pathways involved in TCR gene expression modulation.

Main Methods:

  • Treatment of Jurkat T cells with phorbol 12-myristate 13-acetate (PMA) and other T cell activators.
  • Analysis of surface TCR-alpha/beta/CD3 complex expression.
  • Measurement of TCR-alpha and -beta mRNA levels using quantitative techniques.
  • Run-on transcription assays to assess gene transcription rates.
  • Inhibition of protein synthesis using cycloheximide.

Main Results:

  • PMA treatment decreased surface TCR-alpha/beta/CD3 complex expression.
  • PMA induced significant increases in TCR-alpha and -beta mRNA levels, peaking at 12 hours.
  • Only protein kinase C activators induced TCR-alpha and -beta gene expression.
  • Elevated TCR gene expression correlated with decreased c-myc proto-oncogene expression.
  • PMA-induced mRNA increases were due to enhanced gene transcription rates.
  • Protein synthesis is not required for the full induction of TCR-alpha and some TCR-beta transcripts.

Conclusions:

  • Protein kinase C activation is a key regulator of TCR-alpha and -beta gene expression in Jurkat T cells.
  • PMA stimulation leads to transcriptional activation of both TCR-alpha and -beta genes.
  • Modulation of TCR expression is linked to changes in c-myc proto-oncogene levels.

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