title: Quantity of HLA-C surface expression and licensing of KIR2DL+ natural killer cells.
abstract: Natural killer (NK) cells require interaction of inhibitory surface receptors with human leukocyte antigen (HLA) ligands during development to acquire functional competence in a process termed "licensing." The quantity of HLA required for this process is unknown. Two polymorphisms affecting HLA-C surface expression (rs9264942 and rs67384697) have recently been identified, and shown to influence progression of HIV infection. We typed a cohort of healthy donors for the two HLA-C-related polymorphisms, KIR2DL1 and KIR2DL3, and their respective HLA-C ligands and analyzed how HLA ligands influenced licensing status of killer cell immunoglobulin-like receptor (KIR)+ NK cells in terms of degranulation and cytokine production in response to HLA-deficient target cells. The presence of respective HLA class I ligands increased the function of KIR2DL1+ and KIR2DL3+ NK cells in a dose-dependent manner. In contrast, neither of the HLA-C-related polymorphisms nor the quantity of cell surface HLA-C had any significant effect on NK cell function. Interestingly, HLA-Cw7-an HLA-C allele with low surface expression-licensed KIR2DL3+ NK cells more strongly than any other KIR2DL3 ligand. The quantity of cell surface HLA-C does not appear to influence licensing of NK cells, and the HLA-C-related polymorphisms presumably influence HIV progression through factors unrelated to NK cell education.
authors: Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031, Basel, Switzerland.
authors: Hojjatollah Nozad
authors: HN
authors: Charoudeh
authors: Laurent
authors: L
authors: Schmied
authors: Asensio
authors: A
authors: Gonzalez
authors: Grzegorz
authors: G
authors: Terszowski
authors: Karol
authors: K
authors: Czaja
authors: Karin
authors: K
authors: Schmitter
authors: Laura
authors: L
authors: Infanti
authors: Andreas
authors: A
authors: Buser
authors: Martin
authors: M
authors: Stern
mesh_terms: D004247:DNA / Q000235:genetics; D005838:Genotype; D015658:HIV Infections; D015236:HLA-C Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D007962:Leukocytes; D008024:Ligands; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D054340:Receptors, KIR / Q000235:genetics* / Q000378:metabolism; D054342:Receptors, KIR2DL1 / Q000235:genetics* / Q000378:metabolism; D054343:Receptors, KIR2DL2 / Q000235:genetics* / Q000378:metabolism; D054344:Receptors, KIR2DL3 / Q000235:genetics* / Q000378:metabolism
chemical_list: D015236:HLA-C Antigens; D008024:Ligands; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3; D004247:DNA