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Published on: January 22, 2019
CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity
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
Summary
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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