Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses.
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-gamma secretion and CD107a degranulation assays than its counterpart in HLA-C2 homozygous subjects. The differential IFN-gamma 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.
Ahlenstiel
Golo
G
Immunology Section, Liver Diseases Branch, NIDDK, NIH, Bethesda, Maryland 20892-1800, USA.
Martin
Maureen P
MP
Gao
Xiaojiang
X
Carrington
Mary
M
Rehermann
Barbara
B
D015550:Cell Degranulation; D005260:Female; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D054340:Receptors, KIR / Q000235:genetics / Q000502:physiology*
D015236:HLA-C Antigens; D054340:Receptors, KIR; D007371:Interferon-gamma