Stepwise progression of β-selection during T cell development involves histone deacetylation.

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^Pre" stage, CD5 and Lef1 are up-regulated to reflect pre-TCR signalling, and their expression correlates with prol

SUBMITTER: Chann AS 

PROVIDER: S-EPMC9595210 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature