αβ versus γδ lineage choice at the first TCR-controlled checkpoint

αβ and γδ T cells develop in the thymus from a common precursor. Although lineages initially were defined by the type of TCR they express, it soon became clear that the TCR type per se does not play a deterministic role in the lineage decision, since in various transgenic and knockout models, as well as in a small fraction of cells in wt mice, the TCRγδ can drive the differentiation of αβ lineage cells and the TCRαβ can drive differentiation of γδ lineage cells. Thus until recently it was unclear what determines lineage choice and at which stage the two lineages diverge. Recent observations suggest that TCR signal strength determines lineage fate and that lineage choice is made at or shortly after the first TCR-controlled checkpoint. While it is clear that the decision between αβ and γδ lineages is made at the first TCR-controlled checkpoint and the αβ sublineages split off later, it is less clear whether γδ sublineages divert already at the first TCR-controlled checkpoint or later. Recent experiments support the former view.