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

Malte Deseke, Francesca Rampoldi, Inga Sandrock, Eva Borst, Heike Böning, George Liam Ssebyatika, Carina Jürgens, Nina Plückebaum, Maleen Beck, Ahmed Hassan, Likai Tan, Abdi Demera, Anika Janssen, Peter Steinberger, Christian Koenecke, Abel Viejo-Borbolla, Martin Messerle, Thomas Krey, Immo Prinz*

*Corresponding author for this work
5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere20212525
JournalJournal of Experimental Medicine
Volume219
Issue number9
ISSN0022-1007
DOIs
Publication statusPublished - 05.09.2022

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Center for Structural and Cell Biology (CSCM/ZMSZ)

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