Anti-Cd8b1 Monoclonal antibody, Alexa Fluor® 488

The differentiation and function of peripheral helper and cytotoxic T cell lineages is coupled with the expression of CD4 and CD8 coreceptor molecules, respectively. This indicates that the control of coreceptor gene expression is closely linked with the regulation of CD4/CD8 lineage decision of DP thymocytes. Research performed during the last two decades revealed comprehensive mechanistic insight into the developmental stage- and subset/lineage-specific regulation of Cd4, Cd8a and Cd8b1 (Cd8) gene expression. These studies provided important insight into transcriptional control mechanisms during T cell development and into the regulation of cis-regulatory networks in general. Moreover, the identification of transcription factors involved in the regulation of CD4 and CD8 significantly advanced the knowledge of the transcription factor network regulating CD4/CD8 cell-fate choice of DP thymocytes. In this review, we provide an overview of the identification and characterization of CD4/CD8 cis-regulatory elements and present recent progress in our understanding of how these cis-regulatory elements control CD4/CD8 expression during T cell development and in peripheral T cells. In addition, we describe the transcription factors implicated in the regulation of coreceptor gene expression and discuss how these factors are integrated into the transcription factor network that regulates CD4/CD8 cell-fate choice of DP thymocytes.

Coreceptor expression is tightly regulated during thymocyte development. Deletion of specific Cd8 enhancers leads to variegated expression of CD8 alpha beta heterodimers in double-positive thymocytes. Here we show CD8 variegation is correlated with an epigenetic 'off' state, linking Cd8 enhancer function with chromatin remodeling of the adjacent genes Cd8a and Cd8b1 ( Cd8). The zinc finger protein MAZR bound the Cd8 enhancer and interacted with the nuclear receptor corepressor N-CoR complex in double-negative thymocytes. MAZR was downregulated in double-positive and CD8 single-positive thymocytes. 'Enforced' expression of MAZR led to impaired Cd8 activation and variegated CD8 expression. Our results demonstrate epigenetic control of the Cd8 loci and identify MAZR as an important regulator of Cd8 expression.