TCR Signal Strength Influences αβ/γδ Lineage Fate

Summary: Signals transduced by T cell antigen receptors (TCRs) have been shown to be critical for αβ and γδ T cell development, but their role in lineage determination remains poorly defined. Two models have been forwarded for αβ/γδ 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 γδTCR. We then analyzed the impact of TCR signal strength on αβ/γδ lineage development by altering the surface expression or signaling potential of the γδTCR complex. We found that increasing the γδTCR signal strength favored γδ lineage development, whereas weakening the γδTCR signal favored αβ lineage development. These results support a model in which the strength of the TCR signal is a critical determinant in the lineage fate decision. [Copyright &y& Elsevier]