Stable Frequencies of HLA-C(*)03:04/Peptide-Binding KIR2DL2/3(+) Natural Killer Cells Following Vaccination

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-NS2A(4−13)-tetramer bound to a larger proportion of KIR2DL2/3(+) NK cells compared to HIV-1/HLA-C(*)03:04-Gag(296−304)- or HCV/HLA-C(*)03:04-Core(136−144)-tetramers. The YFV/HLA-C(*)03:04-NS2A(4−13)-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.