TCR and Notch synergize in αβ versus γδ lineage choice

At two checkpoints, T cell development is controlled by T cell receptor (TCR) signaling, which determines survival and lineage commitment. At the first of these checkpoints, signaling by the pre-TCR, the gamma delta TCR or the alpha beta TCR has a major but nonexclusive impact on whether cells will become CD4(-)CD8(-) gamma delta or CD4(+)CD8(+) alpha beta lineage cells. Pre-TCR signals synergize with moderate Notch signals to generate up lineage cells. Relatively strong signals by the gamma delta TCR (or early expressed alpha beta TCR) in the absence of Notch signaling are sufficient to yield gamma delta lineage cells. However, relatively weak signals of the latter two receptors combined with strong Notch signaling result in the formation of alpha beta lineage cells that generate a diverse alpha beta TCR repertoire in pre-TCR-deficient mice. It remains to be determined whether TCR and/or Notch signals instruct or confirm predetermined lineage fate.