Two major T lymphocyte lineages--alphabeta and gammadelta T cells--develop in the thymus from common precursors. Differentiation of both lineages requires signals coming from TCRs. Development of alphabeta T cells is driven at early stages by signaling from the pre-TCR, most likely in a ligand-independent fashion, and later--by signals delivered by alphabetaTCRs binding to their ligands--classical or non-classical MHC molecules. gammadelta lineage cells likewise require TCR signaling for their differentiation. Recent work from several groups suggests that TCR signaling not only ensures the developmental progression towards alphabeta and gammadelta lineages but that signal strength instructs lineage fate: weaker TCR signal results in alphabeta and stronger--in gammadelta lineage commitment. However, as most gammadeltaTCRs remain orphan receptors, it is still debated whether strong signals from gammadeltaTCRs in development are generated in a ligand-dependent manner (as in the case of alphabetaTCRs), ligand-independent manner (as for pre-TCR) or both. Here we summarize evidence supporting a possible role for ligands in gammadelta T cell lineage commitment and the generation of gammadelta sublineages.
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