TCR and Notch synergize in alphabeta versus gammadelta lineage choice

Abstract

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 gammadeltaTCR or the alphabetaTCR has a major but nonexclusive impact on whether cells will become CD4-CD8- gammadelta or CD4+CD8+ alphabeta lineage cells. Pre-TCR signals synergize with moderate Notch signals to generate alphabeta lineage cells. Relatively strong signals by the gammadeltaTCR (or early expressed alphabetaTCR) in the absence of Notch signaling are sufficient to yield gammadelta lineage cells. However, relatively weak signals of the latter two receptors combined with strong Notch signaling result in the formation of alphabeta lineage cells that generate a diverse alphabetaTCR repertoire in pre-TCR-deficient mice. It remains to be determined whether TCR and/or Notch signals instruct or confirm predetermined lineage fate.