Role of a selecting ligand in shaping the murine gamma delta-TCR repertoire

Unlike alpha beta-T lineage cells, where the role of ligand in intrathymic selection is well established, the role of ligand in the development of gamma delta-T cells remains controversial. Here we provide evidence for the role of a bona fide selecting ligand in shaping the gamma delta-T cell-receptor (TCR) repertoire. Reactivity of the gamma delta-TCR with the major histocompatibility complex (MHC) Class Ib ligands, H2-T10/22, is critically dependent upon the EGYEL motif in the complementarity determining region 3 (CDR3) of TCR delta. In the absence of H2-T10/22 ligand, the commitment of H2-T10/22 reactive gamma delta-T cells to the gamma delta fate is diminished, and the specification of those gamma delta committed cells to the IFN-gamma or interleukin-17 effector fate is altered. Furthermore, those cells that do adopt the gamma delta fate and mature exhibit a profound alteration in the gamma delta TCR repertoire, including depletion of the EGYEL motif and reductions in both CDR3 delta length and charge. Taken together, these data suggest that ligand plays an important role in shaping the TCR repertoire of gamma delta-T cells.