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

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.

authors

Fahl SP,Coffey F,Kain L,Zarin P,Dunbrack RL Jr,Teyton L,Zúñiga-Pflücker JC,Kappes DJ,Wiest DL

doi

10.1073/pnas.1718328115

subject

Has Abstract

pub_date

2018-02-20 00:00:00

pages

1889-1894

issue

8

eissn

0027-8424

issn

1091-6490

pii

1718328115

journal_volume

115

pub_type

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