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

Unlike αβ-T lineage cells, where the role of ligand in intrathymicselection is well established, the role of ligand in the developmentQ:11 of γδ-T cells remains controversial. Here we provide evidence forthe role of a bona fide selecting ligand in shaping the γδ-T cellreceptor(TCR) repertoire. Reactivity of the γδ-TCR with the majorhistocompatibility complex (MHC) Class Ib ligands, H2-T10/22, iscritically dependent upon the EGYEL motif in the complementaritydetermining region 3 (CDR3) of TCRδ. In the absence of H2-T10/22 ligand, the commitment of H2-T10/22 reactive γδ-T cells to theγδ fate is diminished, and the specification of those γδ committedcells to the IFN-γ or interleukin-17 effector fate is altered. Furthermore,those cells that do adopt the γδ fate and mature exhibit aprofound alteration in the γδTCR repertoire, including depletion ofthe EGYEL motif and reductions in both CDR3δ length and charge.Taken together, these data suggest that ligand plays an importantrole in shaping the TCR repertoire of γδ-T cells.