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

Autor: Deseke, Malte, Rampoldi, Francesca, Sandrock, Inga, Borst, Eva, Böning, Heike, Ssebyatika, George Liam, Jürgens, Carina, Plückebaum, Nina, Beck, Maleen, Hassan, Ahmed, Tan, Likai, Demera, Abdi, Janssen, Anika, Steinberger, Peter, Koenecke, Christian, Viejo-Borbolla, Abel, Messerle, Martin, Krey, Thomas, Prinz, Immo
Zdroj: The Journal of Experimental Medicine; September 2022, Vol. 219 Issue: 9 pe20212525-e20212525, 1p
Abstrakt: 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.
Databáze: Supplemental Index