Stepwise progression of beta-selection during T cell development involves histone deacetylation
- Author(s)
- Chann, AS; Charnley, M; Newton, LM; Newbold, A; Wiede, F; Tiganis, T; Humbert, PO; Johnstone, RW; Russell, SM;
- Journal Title
- Life Science Alliance
- Publication Type
- Research article
- Abstract
- During T cell development, the first step in creating a unique T cell receptor (TCR) is genetic recombination of the TCRbeta chain. The quality of the new TCRbeta is assessed at the beta-selection checkpoint. Most cells fail this checkpoint and die, but the coordination of fate at the beta-selection checkpoint is not yet understood. We shed new light on fate determination during beta-selection using a selective inhibitor of histone deacetylase 6, ACY1215. ACY1215 disrupted the beta-selection checkpoint. Characterising the basis for this disruption revealed a new, pivotal stage in beta-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 proliferation. These findings suggest a refined model of beta-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 beta-selection checkpoint.
- Publisher
- Life Science Alliance
- Keywords
- *CD28 Antigens/genetics/metabolism; *Receptors, Antigen, T-Cell, alpha-beta/genetics; Histones/metabolism; Histone Deacetylase 6/metabolism; T-Lymphocytes/metabolism; Receptors, Antigen, T-Cell/metabolism
- Department(s)
- Laboratory Research
- PubMed ID
- 36283704
- Publisher's Version
- https://doi.org/10.26508/lsa.202201645
- Open Access at Publisher's Site
https://doi.org/10.26508/lsa.202201645- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-04-04 06:09:39
Last Modified: 2023-04-17 11:53:04