The impact of pre-T-cell receptor signals on gene expression in developing T cells.

Abstract

The pre-T-cell receptor (pre-TCR), which is composedof the pre-TCR-α (pTα) and TCR-β chains, is the first receptor in the development of αβ T cells that associateswith signal-transducing CD3 molecules and mediates themost effective entry into the αβ lineage. The pre-TCR,which signals via a signaling cascade similar to that of theαβ TCR, is also absolutely essential for TCRβ allelic exclusion, even though signals that determine entry into theCD4+8+ compartment of thymocytes and that mediate allelic exclusion bifurcate below the adapter protein SLP76. The pre-TCR takes away from the γδ-lineage cellswith productive TCRβ rearrangements and may thus instruct entry into the αβ lineage. It is mostly, if not exclusively, expressed on the surface of developing thymocytes as a heterodimer, utilizing the long pTα form withone extracellular immunoglobulin (Ig)-like domain.Some experiments suggest that the pre-TCR spontaneously localizes together with glycolipid-enrichedmembrane domains and may signal in a cell-autonomousfashion without binding to a ligand. Thus, the pre-TCRαprotein may not represent a mere TCRα surrogate chain,but a protein that in association with the TCRβ chain actsas a cell-autonomous developmental switch...