Stepwise progression of ß-selection during T cell development involves histone deacetylation.
Life Sci Alliance
; 6(1)2023 01.
Article
em En
| MEDLINE
| ID: mdl-36283704
ABSTRACT
During T cell development, the first step in creating a unique T cell receptor (TCR) is genetic recombination of the TCRß chain. The quality of the new TCRß is assessed at the ß-selection checkpoint. Most cells fail this checkpoint and die, but the coordination of fate at the ß-selection checkpoint is not yet understood. We shed new light on fate determination during ß-selection using a selective inhibitor of histone deacetylase 6, ACY1215. ACY1215 disrupted the ß-selection checkpoint. Characterising the basis for this disruption revealed a new, pivotal stage in ß-selection, bookended by up-regulation of TCR co-receptors, CD28 and CD2, respectively. Within this "DN3bPre" 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 ß-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 ß-selection checkpoint.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T alfa-beta
/
Antígenos CD28
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article