Branching out to gain control: how the pre-TCR is linked to multiple functions
✍ Scribed by Ada M Kruisbeek; Mariëlle C Haks; Michael Carleton; David L Wiest; Alison M Michie; Juan Carlos Zúñiga-Pflücker
- Publisher
- Elsevier Science
- Year
- 2000
- Tongue
- English
- Weight
- 131 KB
- Volume
- 21
- Category
- Article
- ISSN
- 0167-5699
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✦ Synopsis
evelopment of T cells with an ␣ T-cell receptor (TCR) is regulated with great precision by what could be regarded as a developmental forerunner of the TCR, the so-called pre-TCR. This receptor triggers signals for survival, expansion and differentiation in pre-T cells, but the molecular events controlled by the pre-TCR remain ill-defined. How are the pre-TCR signals that lead to survival distinguished from those that lead to proliferation or inhibition of rearrangements at the TCR locus? We argue that pre-T cells that have received survival signals from the pre-TCR do not unfold a pre-existing imprinted program of proliferation and differentiation. Rather, pre-TCR-driven signals play an instructive role in promoting development of double-positive (DP) thymocytes, and the pre-TCR signaling pathway required for cessation of TCR chain rearrangements is distinct from that which regulates other aspects of ␣ T-cell development. Pre-TCR-driven selection of ␣ T-cell fate thus emerges as a multi-branched process in which the different cell-fate decisions are orchestrated by different signaling pathways.