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

A rearranged TCR alpha 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-TCR alpha (pT alpha) expression, In normal C57BL/6 thymocytes, TCR alpha expression is not detected in DN thymocytes while, in contrast, TCR beta expression is initiated at the most immature c-kit(+)CD44(+)CD25(-) stage and continues throughout thymocyte development, pT alpha 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 TCR beta and pT alpha expression are independent, the pre-TCR complex mediates signals controlling the appearance of alpha beta TCR through selective regulation of TCR alpha and pT alpha genes.