05/09/2022
The Journal of experimental medicine
A CMV-induced adaptive human V_1+ __ T cell clone recognizes HLA-DR
The innate and adaptive roles of __ T cells and their clonal __ T cell receptors (TCRs) in immune responses are still unclear. Recent studies of __ TCR repertoire dynamics showed massive expansion of individual V_1+ __ 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 V_3V_1+ TCR, and further characterization revealed a direct interaction of this V_1+ TCR with the MHC II complex HLA-DR. Since MHC II is strongly upregulated by interferon-_, these results suggest an inflammation-induced MHC-dependent immune response of __ T cells.
05/09/2022
The Journal of experimental medicine
A CMV-induced adaptive human Vδ1+ γδ T cell clone recognizes HLA-DR
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.