在胸腺细胞成熟过程中，从TCRδ增强子功能到TCRα增强子功能的发育性转变。

A developmental switch from TCR delta enhancer to TCR alpha enhancer function during thymocyte maturation.

作者信息

Hernández-Munain C, Sleckman B P, Krangel M S

机构信息

Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.

出版信息

Immunity. 1999 Jun;10(6):723-33. doi: 10.1016/s1074-7613(00)80071-0.

DOI:10.1016/s1074-7613(00)80071-0

PMID:10403647

Abstract

V(D)J recombination and transcription within the TCR alpha/delta locus are regulated by three characterized cis-acting elements: the TCR delta enhancer (Edelta), TCR alpha enhancer (Ealpha), and T early alpha (TEA) promoter. Analysis of enhancer and promoter occupancy and function in developing thymocytes in vivo indicates Edelta and Ealpha to be developmental-stage-specific enhancers, with Edelta "on" and Ealpha "off" in double-negative III thymocytes and Edelta "off" and Ealpha "on" in double-positive thymocytes. Edelta downregulation reflects a loss of occupancy. Surprisingly, Ealpha and TEA are extensively occupied even prior to activation. TCR delta downregulation in double-positive thymocytes depends on two events, Edelta inactivation and removal of TCR delta from the influence of Ealpha by chromosomal excision.

摘要

TCRα/δ基因座内的V(D)J重组和转录由三个已明确的顺式作用元件调控：TCRδ增强子（Edelta）、TCRα增强子（Ealpha）和T早期α（TEA）启动子。对体内发育中的胸腺细胞中增强子和启动子占据情况及功能的分析表明，Edelta和Ealpha是发育阶段特异性增强子，在双阴性III胸腺细胞中Edelta“开启”而Ealpha“关闭”，在双阳性胸腺细胞中Edelta“关闭”而Ealpha“开启”。Edelta的下调反映了占据情况的丧失。令人惊讶的是，即使在激活之前，Ealpha和TEA也被大量占据。双阳性胸腺细胞中TCRδ的下调取决于两个事件，即Edelta失活以及通过染色体切除将TCRδ从Ealpha的影响中去除。