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Related Experiment Videos

Ceramide-induced TCR up-regulation.

C Menné1, J P Lauritsen, J Dietrich

  • 1Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark.

Journal of Immunology (Baltimore, Md. : 1950)
|September 7, 2000
PubMed
Summary

T-cell receptor (TCR) recycling influences T cell activation. This study reveals ceramide up-regulates TCR expression by affecting recycling dynamics, potentially enhancing T cell responsiveness.

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • T-cell receptor (TCR) is a constitutively recycling receptor.
  • Protein kinase C activity modulates TCR recycling kinetics, affecting surface expression and T cell activation.
  • TCR down-regulation compromises T cell activation, while up-regulation is expected to increase responsiveness.

Purpose of the Study:

  • To identify and characterize pathways for T-cell receptor (TCR) up-regulation.
  • To investigate the role of ceramide in modulating TCR recycling and surface expression.

Main Methods:

  • Investigated ceramide's effect on TCR recycling dynamics and surface expression.
  • Utilized phosphatase inhibitors to explore underlying mechanisms.
  • Analyzed T cell variants to identify key molecular motifs involved in TCR up-regulation.

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Main Results:

  • Ceramide induced T-cell receptor (TCR) up-regulation in a concentration- and time-dependent manner.
  • Ceramide-induced TCR up-regulation was mediated by serine/threonine protein phosphatase 2A.
  • TCR up-regulation depended on an intact CD3gamma L-based motif within the TCR recycling pathway.

Conclusions:

  • Ceramide modulates T-cell receptor (TCR) recycling kinetics, leading to TCR up-regulation.
  • This up-regulation enhances T cell responsiveness, suggesting a physiological role.
  • T cells can adjust TCR expression levels to modulate their responsiveness.