T cell receptor-instructed αβ versus γδ lineage commitment revealed by single-cell analysis

alpha beta and gamma delta T cell lineages develop in the thymus from a common precursor. It is unclear at which stage of development commitment to these lineages takes place and in which way T cell receptor signaling contributes to the process. Recently, it was demonstrated that strong TCR signals favor gamma delta lineage development, whereas weaker TCR signals promote alpha beta lineage fate. Two models have been proposed to explain these results. The first model suggests that commitment occurs after TCR expression and TCR signaling directly instructs lymphocytes to adopt one or the other lineage fate. The second model suggests that commitment occurs before TCR expression and that TCR signaling merely confirms the lineage choice. By tracing the fate of single T cell precursors, this study shows that there is no commitment to either the alpha beta or gamma delta lineage before TCR expression and that modulation of TCR signaling in progeny of a single TCR- expressing cell changes lineage commitment.