Pre-TCR signaling components trigger transcriptional activation of a rearranged TCRα gene locus and silencing of the pre-TCRα locus: Implications for intrathymic differentiation

Abstract

A rearranged TCR α transgene remains transcriptionally inactive in rag-2(-/-) thymocytes but can be induced by CD3-mediated signals with concomitant maturation of double-negative (DN) thymocytes to the CD4+CD8+ double-positive (DP) stage. Reciprocally, the same signals silence pre-TCRα (pTα) expression. In normal C57BL/6 thymocytes, TCRα expression is not detected in DN thymocytes while, in contrast, TCRβ expression is initiated at the most immature c-kit+CD44+CD25- stage and continues throughout thymocyte development. pTα expression is first detected at the intermediate c-kit(±)CD44+CD25+ DN stage, increases during transition to the more mature c-kit-CD44-CD25+ stage and is lost at the DP stage. Thus, although TCRβ and pTα expression are independent, the pre-TCR complex mediates signals controlling the appearance of αβ TCR through selective regulation of TCRα and pTα genes.