Ganesan, Sridharan Höglund, Petter Data_Sheet_1_Inhibitory Receptor Crosslinking Quantitatively Dampens Calcium Flux Induced by Activating Receptor Triggering in NK Cells.PDF <p>Natural killer (NK) cell function is regulated by a balance between activating and inhibitory receptors, but the details of this receptor interplay are not extensively understood. We developed a flow cytometry-based assay system in which Ca<sup>2+</sup> flux downstream of antibody-mediated activating receptor triggering was studied in the presence or absence of inhibitory receptor co-crosslinking. We show that the inhibitory influence on activating receptor-induced Ca<sup>2+</sup> flux is quantitatively regulated, both on murine and human NK cells. Furthermore, both activating and inhibitory receptors operate in an additive way, suggesting that a fine-tuned balance between activating and inhibitory receptors regulate proximal NK cell signaling. We also demonstrate that murine NK cell expression of H2D<sup>d</sup> lowered the capacity of Ly49A to deliver inhibitory signals after antibody crosslinking, suggesting that the cis interaction between H2D<sup>d</sup> and Ly49A reduce the signaling capacity of Ly49A in this setting. Finally, we show that priming of NK cells by IL-15 rapidly augments Ca<sup>2+</sup> flux after activating receptor signaling without attenuating the potential of inhibitory receptors to reduce Ca<sup>2+</sup> flux. Our data shed new light on NK cell inhibition and raises new questions for further studies.</p> NK cells;MHC class I;calcium flux;Ly49;NKG2A;inhibition;IL-15;quantitative 2019-01-14
    https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_Inhibitory_Receptor_Crosslinking_Quantitatively_Dampens_Calcium_Flux_Induced_by_Activating_Receptor_Triggering_in_NK_Cells_PDF/7582457
10.3389/fimmu.2018.03173.s001