Research ArticleImmunology

PreTCR and TCRγδ Signal Initiation in Thymocyte Progenitors Does Not Require Domains Implicated in Receptor Oligomerization

Science Signaling  19 Jul 2011:
Vol. 4, Issue 182, pp. ra47
DOI: 10.1126/scisignal.2001765

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Driving Thymocyte Development

The development of thymocytes into two different classes of T cells, as defined by their T cell receptors (TCRs), depends on the abundance of distinct TCR chains (αβ versus γδ) at the cell surface and on the relative strengths of the signals generated by these receptors. Signal initiation at the point at which cell fate is determined (the β checkpoint) is ligand-independent and thought to be a result of the oligomerization of TCRs, which triggers downstream signaling. However, Mahtani-Patching et al. showed that thymocytes expressing preTCR (the precursor of αβ) or γδ TCRs devoid of the extracellular domains or residues previously implicated in receptor oligomerization can still drive thymocytes through the β selection checkpoint. Furthermore, thymocytes expressing TCRγδ that lacked all of their extracellular immunoglobulin domains also underwent signal initiation. Together, these findings suggest that thymocyte cell fate is controlled by the relative abundance of the appropriate TCR chains at the cell surface, rather than by their oligomerization.