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International Immunology, Vol 9, 1475-1480, Copyright © 1997 by Oxford University Press


ARTICLES

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

S Koyasu, LK Clayton, A Lerner, H Heiken, A Parkes and EL Reinherz
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA, USA.

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.
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