Institute of Immunology, Hannover Medical School, Hannover, Germany.
Excellence Cluster 2155 RESIST, Hannover Medical School, Hannover, Germany.
J Exp Med. 2022 Sep 5;219(9). 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.
γδ T 细胞及其克隆 γδ T 细胞受体（TCR）在免疫反应中的先天和适应性作用仍不清楚。最近对 γδ TCR 库动力学的研究表明，在病毒感染期间，个体 Vδ1+ γδ T 细胞克隆会大量扩增。为了判断这种扩增是随机的还是实际上代表 TCR 依赖性适应性免疫反应，需要有关其同源 TCR 配体的信息。在这里，我们使用 CRISPR/Cas9 介导的筛选来鉴定 HLA-DRA、RFXAP、RFX5 和 CIITA 是识别 CMV 诱导的 Vγ3Vδ1+ TCR 的靶细胞所必需的，进一步的表征揭示了该 Vδ1+ TCR 与 MHC II 复合物 HLA-DR 的直接相互作用。由于 MHC II 被干扰素-γ强烈上调，这些结果表明 γδ T 细胞的炎症诱导的 MHC 依赖性免疫反应。
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