AI Article Synopsis

  • γδ T cells play both innate and adaptive roles in immune responses, but their specific mechanisms, especially regarding their T cell receptors (TCRs), remain unclear.
  • Recent findings show a significant expansion of specific Vδ1+ γδ T cell clones during viral infections, raising questions about whether this response is random or TCR-dependent.
  • Using CRISPR/Cas9, researchers identified key molecules necessary for these T cells to recognize targets and demonstrated that the Vδ1+ TCR interacts directly with the MHC II complex, suggesting that inflammation can enhance γδ T cell responses through MHC-dependent mechanisms.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301659PMC
http://dx.doi.org/10.1084/jem.20212525DOI Listing

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