A CMV-induced adaptive human Vδ1+ γδ T cell clone recognizes HLA-DR

J Exp Med. 2022 Sep 5;219(9):e20212525. doi: 10.1084/jem.20212525. Epub 2022 Jul 19.


The innate and adaptive roles of γδ T cells and their clonal γδ T cell receptors (TCRs) in immune responses are still unclear. Recent studies of γδ TCR repertoire dynamics showed massive expansion of individual Vδ1+ γδ T cell clones during viral infection. To judge whether such expansion is random or actually represents TCR-dependent adaptive immune responses, information about their cognate TCR ligands is required. Here, we used CRISPR/Cas9-mediated screening to identify HLA-DRA, RFXAP, RFX5, and CIITA as required for target cell recognition of a CMV-induced Vγ3Vδ1+ TCR, and further characterization revealed a direct interaction of this Vδ1+ TCR with the MHC II complex HLA-DR. Since MHC II is strongly upregulated by interferon-γ, these results suggest an inflammation-induced MHC-dependent immune response of γδ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clone Cells
  • Cytomegalovirus Infections*
  • HLA-DR Antigens
  • Humans
  • Intraepithelial Lymphocytes*
  • Receptors, Antigen, T-Cell, gamma-delta
  • T-Lymphocyte Subsets


  • HLA-DR Antigens
  • Receptors, Antigen, T-Cell, gamma-delta