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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity

H S Azzam1, A Grinberg, K Lui

  • 1Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.

The Journal of Experimental Medicine
|December 22, 1998
PubMed

Insights

CD5 glycoprotein negatively regulates T cell receptor (TCR) signaling. Its surface expression is modulated during T cell development, influenced by pre-TCR engagement and TCR-ligand interactions, fine-tuning immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • CD5 is a cell surface glycoprotein known to negatively regulate T cell receptor (TCR)-mediated signaling.
  • Understanding the regulation of CD5 expression is crucial for comprehending T cell development and function.

Purpose of the Study:

  • To investigate the regulation of CD5 surface expression during thymocyte ontogeny.
  • To determine the factors influencing CD5 expression in mice with developmental or signal transduction defects.

Main Methods:

  • Analysis of CD5 surface expression on thymocytes at various developmental stages (DN, DP, SP).
  • Examination of CD5 regulation in mice with specific genetic or signaling defects.
  • Assessing the role of pre-TCR and TCR-MHC interactions in CD5 modulation.

Main Results:

  • Low CD5 expression on double-negative (DN) thymocytes is TCR gene rearrangement-independent.
  • CD5 induction on DN thymocytes requires pre-TCR engagement and p56(lck) activity.
  • Intermediate CD5 levels at the double-positive (DP) stage correlate with TCR-MHC interaction affinity and signaling capacity.
  • High CD5 expression on DP and single-positive (SP) thymocytes is induced by TCR engagement with selecting ligands.
  • CD5 expression on mature T cells mirrors the avidity/signaling intensity of the TCR-MHC-ligand interaction.

Conclusions:

  • Developmental regulation of CD5 expression is intricately linked to TCR signaling strength and TCR-ligand avidity.
  • CD5 acts as a critical modulator, fine-tuning TCR signaling responses throughout T cell maturation.
  • These findings provide insights into the mechanisms controlling T cell sensitivity and activation thresholds.

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