It is shown that intracellular pAg accumulation can modulate binding of Vγ9Vδ2+ TCR in a BTN3A1-dependent manner, indicating the important role of TCR binding to BTN3A1 in pAg recognition.
Abstract
Phosphoantigen (pAg) recognition by Vγ9Vδ2+ T cells plays a critical role in immunity to pathogens and cancer. The butyrophilin (BTN) family of molecules have emerged as key regulators of γδ T cells; however, the underlying mechanisms remain unclear. Here, we demonstrate an interaction between BTN3A1 and Vγ9Vδ2+ T cell receptor (TCR) in a cell-free assay, confirming that BTN3A1 is a direct ligand for the Vγ9Vδ2+ TCR. Furthermore, immobilized recombinant BTN2A1 plus BTN3A1 extracellular domains are sufficient to activate Vδ2+ T cells. Finally, we show that intracellular pAg accumulation can modulate binding of Vγ9Vδ2+ TCR in a BTN3A1-dependent manner, indicating the important role of TCR binding to BTN3A1 in pAg recognition. These data confirm that BTN3A1, in conjunction with BTN2A1, is a direct ligand for Vγ9Vδ2+ TCR, providing the key interactions required for pAg recognition.
The gamma delta T-cell receptor (γδ TCR) mediates γδ T-cell responses that are crucial for immune defense, tissue surveillance, and homeostasis. While recent studies suggest that γδ TCRs engage ligands multivalently, how multivalent engagement activates the γδ TCR remains elusive. Here, we present the structures of the...
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The activation of Vγ9Vδ2 T cells has emerged as a promising modality in cancer immunotherapy. Phosphate and phosphonate prodrugs of Vγ9Vδ2 T cell phosphoantigens have been developed as potent activators of Vγ9Vδ2 T cells that are capable of effectively facilitating lysis of a range of cancer cells in vitro. In this wor...
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ABSTRACT This study presents the discovery and first functional characterization of chicken lipid‐reactive Natural Killer T (NKT)‐like cells, resolving a long‐standing knowledge gap in avian immunology. Using purified TCRVβ2+ lymphocytes, we demonstrate through rigorous experiments combining shRNA‐mediated gene silenci...
Nitin Kamble, Faisal R. Anjum, S. Behboudi· European Journal of Immunolo...· 0 citations
Introduction CD19 is a key B-cell co-receptor that amplifies B-cell receptor (BCR) signaling and tunes B-cell activation thresholds. How the conformation of the CD19 cytoplasmic domain is regulated to restrain basal and BCR-induced signaling remains incompletely understood. We investigated whether the phosphoinositide...
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L. Litzau, Elizabeth K. Wren, Andrew C. Kruse et al.· bioRxiv· 0 citations
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Olga Bautista-Cerecero, P. Hernández-Luis, Pablo Martínez-Vicente et al.· Frontiers in Immunology· 0 citations
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