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Fahl SP , Coffey F , Kain L , Zarin P , Dunbrack RL Jr , Teyton L , Zuniga-Pflucker JC , Kappes DJ , Wiest DL
Role of a selecting ligand in shaping the murine gammadelta-TCR repertoire
Proc Natl Acad Sci U S A. 2018 Feb 20;115(8) :1889-1894
PMID: 29432160    PMCID: PMC5828614    URL: https://www.ncbi.nlm.nih.gov/pubmed/29432160
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Unlike alphabeta-T lineage cells, where the role of ligand in intrathymic selection is well established, the role of ligand in the development of gammadelta-T cells remains controversial. Here we provide evidence for the role of a bona fide selecting ligand in shaping the gammadelta-T cell-receptor (TCR) repertoire. Reactivity of the gammadelta-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 TCRdelta. In the absence of H2-T10/22 ligand, the commitment of H2-T10/22 reactive gammadelta-T cells to the gammadelta fate is diminished, and the specification of those gammadelta committed cells to the IFN-gamma or interleukin-17 effector fate is altered. Furthermore, those cells that do adopt the gammadelta fate and mature exhibit a profound alteration in the gammadeltaTCR repertoire, including depletion of the EGYEL motif and reductions in both CDR3delta length and charge. Taken together, these data suggest that ligand plays an important role in shaping the TCR repertoire of gammadelta-T cells.
1091-6490 Fahl, Shawn P Coffey, Francis Kain, Lisa Zarin, Payam Dunbrack, Roland L Jr. Teyton, Luc Zuniga-Pflucker, Juan Carlos Kappes, Dietmar J Wiest, David L Journal Article United States Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):1889-1894. doi: 10.1073/pnas.1718328115. Epub 2018 Feb 5.