Inhibitory KIRs play a central role in regulating NK cell activity. KIR2DL2/3 bind to HLA-C molecules, but the modulation of these interactions by viral infections and presentation of viral epitopes is not well-understood. We investigated whether the frequencies of KIR2DL2/3+ NK cells recognizing HLA-C∗03:04/viral peptide complexes were impacted by YFV vaccination or HIV-1 and HCV infection. Ex vivo HLA class I tetramer staining of primary human NK cells derived from YFV-vaccinated individuals, or HIV-1- or HCV-infected individuals revealed that the YFV/HLA-C∗03:04-NS2A4-13-tetramer bound to a larger proportion of KIR2DL2/3+ NK cells compared to HIV-1/HLA-C∗03:04-Gag296-304- or HCV/HLA-C∗03:04-Core136-144-tetramers. The YFV/HLA-C∗03:04-NS2A4-13-tetramer also exhibited a stronger avidity to KIR2DL2/3 compared to the other tested tetramers. The proportional frequencies of KIR2DL2/3+ NK cells binding to the three tested HLA-C∗03:04 tetramers were identical between YFV-vaccinated individuals or HIV-1- or HCV-infected individuals, and remained stable following YFV vaccination. These data demonstrate consistent hierarchies in the frequency of primary KIR2DL2/3+ NK cells binding HLA-C∗03:04/peptide complexes that were determined by the HLA-C-presented peptide and not modulated by the underlying viral infection or vaccination.
CITATION STYLE
Ziegler, M. C., Grañana, F. B., Garcia-Beltran, W. F., Wiesch, J. S. Z., Hoffmann, C., Rechtien, A., … Altfeld, M. (2018). Stable frequencies of HLA-C∗03:04/peptide-binding KIR2DL2/3+ natural killer cells following vaccination. Frontiers in Immunology, 9(OCT). https://doi.org/10.3389/fimmu.2018.02361
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