γδ and αβ T cell lineage choice: Resolution by a stronger sense of being

A common bipotent thymocyte precursor gives rise to both lineages of T cells, αβ and γδ. However, the cell intrinsic and extrinsic factors that influence αβ- versus γδ-lineage bifurcation remain controversial. γδ T cells play a unique and vital role in host defense, from maintaining integrity at epithelial and mucosal barriers to their newly defined role as an important innate source of interleukin-17. Although a T cell receptor (TCR)-independent fate choice may take place, emerging data supports a model in which the differential signaling capacity of αβ and γδTCRs play an instructional role in specifying lineage fate, with strength of signal measured by the amount of ERK/MAPK pathway activation. Here we discuss how the interplay between intrinsic TCR signals and cell extrinsic signals provided by Notch and TCR ligands help to assign and support a final lineage fate decision.