HIV protective KIR3DL1 and HLA-B genotypes influence NK cell function following stimulation with HLA-devoid cells.
Epidemiological studies in humans have implicated carriage of combinations of genes encoding certain KIR3DL1 (killer Ig-like receptor 3DL1) alleles and their HLA-Bw4 ligands in slower progression to AIDS, lower viral load and protection from infection. Given that the KIR3DL1*h/*y/HLA-B*57 genetic combination is strongly associated with favorable HIV outcomes, we measured responses from NK cells isolated from these individuals by multiparametric flow cytometry for cytokine secretion and degranulation in response to stimulation with HLA-devoid cells to assess whether the KIR/HLA compound genotypes linked to better HIV outcome favor increased NK cell functional potential. Our results indicate that NK cells from these individuals had increased functional potential, particularly in the KIR3DL1(+) NK cell subset. These results support a link between KIR/HLA genotypes and NK cell function and could provide an explanation for the observation that some KIR/HLA combinations are associated protective phenotypes in the context of host-HIV interactions.
Boulet
Salix
S
Division of Clinical Immunology, Research Institute of the McGill University Health Centre, McGill University, Canada.
Song
Rujun
R
Kamya
Philomena
P
Bruneau
Julie
J
Shoukry
Naglaa H
NH
Tsoukas
Christos M
CM
Bernard
Nicole F
NF
D002461:Cell Line, Transformed; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics* / Q000378:metabolism; D006650:Histocompatibility Testing; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology; D054341:Receptors, KIR3DL1 / Q000235:genetics* / Q000378:metabolism
D015235:HLA-B Antigens; C103707:HLA-B57 antigen; C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1