Beyond alphabeta/gammadelta lineage commitment: TCR signal strength regulates gammadelta T cell maturation and effector fate.

Signaling by the gammadelta T cell receptor (TCR) is required not only for alphabeta/gammadelta lineage commitment but also to activate and elicit effector functions in mature gammadelta T cells. Notably, at both of these stages, the signal delivered by the gammadeltaTCR is more robust than the one delivered by either the preTCR or the alphabetaTCR. Recent studies now provide evidence that signaling by the gammadeltaTCR is also required at other stages during gammadelta T cell development. Remarkably, the strength of the gammadeltaTCR signal also plays a role at these other stages, as evidenced by the findings that genetic manipulation of gammadeltaTCR signal strength affects gammadelta T cell maturation and effector fate. In this review, we discuss how a strong TCR signal is a recurring theme in gammadelta T cell development and activation.