AI Article Synopsis

  • T cell development starts with genetic recombination of the TCRβ chain, which is evaluated at the β-selection checkpoint where most cells fail and die.
  • Researchers used the histone deacetylase 6 inhibitor ACY1215, revealing that it disrupts this checkpoint and highlights a crucial stage called "DN3b."
  • This stage involves up-regulation of certain proteins (TCR, CD28, CD5, Lef1) that influence TCR signaling strength, ultimately leading to successful progression beyond the β-selection checkpoint.

Article Abstract

During T cell development, the first step in creating a unique T cell receptor (TCR) is genetic recombination of the TCRβ chain. The quality of the new TCRβ is assessed at the β-selection checkpoint. Most cells fail this checkpoint and die, but the coordination of fate at the β-selection checkpoint is not yet understood. We shed new light on fate determination during β-selection using a selective inhibitor of histone deacetylase 6, ACY1215. ACY1215 disrupted the β-selection checkpoint. Characterising the basis for this disruption revealed a new, pivotal stage in β-selection, bookended by up-regulation of TCR co-receptors, CD28 and CD2, respectively. Within this "DN3b" stage, CD5 and Lef1 are up-regulated to reflect pre-TCR signalling, and their expression correlates with proliferation. These findings suggest a refined model of β-selection in which a coordinated increase in expression of pre-TCR, CD28, CD5 and Lef1 allows for modulating TCR signalling strength and culminates in the expression of CD2 to enable exit from the β-selection checkpoint.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9595210PMC
http://dx.doi.org/10.26508/lsa.202201645DOI Listing

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