Pre-TCR signaling components trigger transcriptional activation of a rearranged TCRα gene locus and silencing of the pre-TCRα locus: implications for intrathymic differentiation
نویسندگان
چکیده
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 CD4FCD8F 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 ckitFCD44FCD25– stage and continues throughout thymocyte development. pTα expression is first detected at the intermediate c-kitKCD44FCD25F DN stage, increases during transition to the more mature c-kit–CD44–CD25F 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.
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