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

Alpha beta and gamma delta T cells are distinguished by the clonotypic subunits contained within their TCRs. Although the alpha beta TCR has been well characterized, much less is known about the gamma delta TCR. Here, we report that, unlike alpha beta T CRs, most gamma delta TCRs expressed on ex vivo gamma delta T cells lack CD3 delta. Despite this structural difference, signal transduction by the gamma delta TCR is superior to that of the alpha beta TCR, as measured by its ability to induce calcium mobilization, ERK activation, and cellular proliferation. Additionally, the TCR complexes expressed on primary gamma delta T cells contain only zeta zeta homodimers; however, following activation and expansion, Fc epsilon R1 gamma is expressed and is included in the gamma delta TCR complex. These results reveal fundamental differences in the primary structure and signaling potential of the alpha beta- and gamma delta TCR complexes.

No abstract