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.
A CMV-induced adaptive human Vδ1+ γδ T cell clone recognizes HLA-DR
Disclosures: M. Deseke and I. Prinz reported a patent to ASC 15-00694 issued. No other disclosures were reported.
- Award Id(s): VI 762/1-1,405772731,PR727/11-1,SFB900,158989968
- Award Id(s): 390874280
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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; A CMV-induced adaptive human Vδ1+ γδ T cell clone recognizes HLA-DR. J Exp Med 5 September 2022; 219 (9): e20212525. doi: https://doi.org/10.1084/jem.20212525
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