Abstract:
:Unlike αβ-T lineage cells, where the role of ligand in intrathymic selection is well established, the role of ligand in the development of γδ-T cells remains controversial. Here we provide evidence for the role of a bona fide selecting ligand in shaping the γδ-T cell-receptor (TCR) repertoire. Reactivity of the γδ-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 TCRδ. In the absence of H2-T10/22 ligand, the commitment of H2-T10/22 reactive γδ-T cells to the γδ fate is diminished, and the specification of those γδ committed cells to the IFN-γ or interleukin-17 effector fate is altered. Furthermore, those cells that do adopt the γδ fate and mature exhibit a profound alteration in the γδTCR repertoire, including depletion of the EGYEL motif and reductions in both CDR3δ length and charge. Taken together, these data suggest that ligand plays an important role in shaping the TCR repertoire of γδ-T cells.
journal_name
Proc Natl Acad Sci U S Aauthors
Fahl SP,Coffey F,Kain L,Zarin P,Dunbrack RL Jr,Teyton L,Zúñiga-Pflücker JC,Kappes DJ,Wiest DLdoi
10.1073/pnas.1718328115subject
Has Abstractpub_date
2018-02-20 00:00:00pages
1889-1894issue
8eissn
0027-8424issn
1091-6490pii
1718328115journal_volume
115pub_type
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