Double knockout of Id2 & Id3 in developing T cells promotes the development of CD4-CD8- αβ T cell (63.3)

Abstract

Abstract αβ T cell development is regulated by sequential rearrangement and expression of TCRβ and TCRα genes at the DN (CD4-CD8-) and DP (CD4+CD8+) stage, respectively. Expression of TCRβ paired with preTα at the DN stage leads to αβ lineage commitment and differentiation into the DP stage. DP cells undergo TCRα gene rearrangement, resulting in expression and the selection of functional αβTCR. Id3 has been shown to be an important sensor downstream of both preTCR and TCR signals. However, Id3 knockout only leads to a partial block in αβ lineage development, suggesting functional compensation from other Id proteins. To further investigate functions of Id proteins at the preTCR and TCR checkpoints, we simultaneously deleted Id3 and the structurally and functionally related Id2 gene at the early DN stage of T cell development. We find that removal of Id2 and Id3 failed to block T cell development at the preTCR checkpoint although imposed a strong block at the TCR checkpoint. Furthermore, deletion of both Id2 and Id3 promoted development of an aberrant population of αβ T cells that bear DN (CD4-CD8-) phenotype. This genetic system revealed a novel function of Id proteins in regulation of alternative αβ lineages during T cell development. We will present the latest information on characterization of this CD4-CD8- αβ T cell lineage associated with Id2 and Id3 disruption in developing T cells.