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.
Authors
Golo Ahlenstiel, Maureen P. Martin, Xiaojiang Gao, Mary Carrington, Barbara Rehermann
Figure 1
Identification and quantitation of HLA-C–inhibited NK cells by flow cytometry.
Copyright © 2024 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)