Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses

Golo Ahlenstiel, Maureen P. Martin, Xiaojiang Gao, Mary Carrington, Barbara Rehermann

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144 Citations (Scopus)

Abstract

Genetic studies suggest a role for killer cell immunoglobulin-like receptor/HLA (KIR/HLA) compound genotypes in the outcome of viral infections, but functional data to explain these epidemiological observations have not been reported. Using an in vitro model of infection with influenza A virus (IAV), we attribute functional differences in human NK cell activity to distinct KIR/HLA genotypes. Multicolor flow cytometry revealed that the HLA-C-inhibited NK cell subset in HLA-C1 homozygous subjects was larger and responded more rapidly in IFN-γ secretion and CD107a degranulation assays than its counterpart in HLA-C2 homozygous subjects. The differential IFN-γ response was also observed at the level of bulk NK cells and was independent of KIR3DL1/HLA-Bw4 interactions. Moreover, the differential response was not caused by differences in NK cell maturation status and phenotype, nor by differences in the type I IFN response of IAV-infected accessory cells between HLA-C1 and HLA-C2 homozygous subjects. These results provide functional evidence for differential NK cell responsiveness depending on KIR/HLA genotype and may provide useful insights into differential innate immune responsiveness to viral infections such as IAV.
Original languageEnglish
Pages (from-to)1017-1026
Number of pages10
JournalJournal of Clinical Investigation
Volume118
Issue number3
DOIs
Publication statusPublished - 2008

Keywords

  • flow cytometry
  • genotype
  • influenza
  • killer cells

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