Project description:Unlike ??-T lineage cells, where the role of ligand in intrathymic selection is well established, the role of ligand in the development of ??-T cells remains controversial. Here we provide evidence for the role of a bona fide selecting ligand in shaping the ??-T cell-receptor (TCR) repertoire. Reactivity of the ??-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?. In the absence of H2-T10/22 ligand, the commitment of H2-T10/22 reactive ??-T cells to the ?? fate is diminished, and the specification of those ?? committed cells to the IFN-? or interleukin-17 effector fate is altered. Furthermore, those cells that do adopt the ?? fate and mature exhibit a profound alteration in the ??TCR repertoire, including depletion of the EGYEL motif and reductions in both CDR3? length and charge. Taken together, these data suggest that ligand plays an important role in shaping the TCR repertoire of ??-T cells.
