TCR signal strength influences αβ/γδ lineage fate

Signals transduced by T cell antigen receptors (TCRs) have been shown to be critical for alpha beta and gamma delta T cell development, but their role in lineage determination remains poorly defined. Two models have been forwarded for alpha beta/gamma delta lineage choice: the instructive model and the stochastic model. Recent data, however, are inconsistent with either model. In this study, we devised an experimental system in which lineage fate was controlled exclusively by the gamma delta TCR. We then analyzed the impact of TCR signal strength on alpha beta/gamma delta lineage development by altering the surface expression or signaling potential of the gamma delta TCR complex. We found that increasing the gamma delta TCR signal strength favored gamma delta lineage development, whereas weakening the gamma delta TCR signal favored up lineage development. These results support a model in which the strength of the TCR signal is a critical determinant in the lineage fate decision.