title: Functional advantage of educated KIR2DL1(+) natural killer cells for anti-HIV-1 antibody-dependent activation.
abstract: Evidence from the RV144 HIV-1 vaccine trial implicates anti-HIV-1 antibody-dependent cellular cytotoxicity (ADCC) in vaccine-conferred protection from infection. Among effector cells that mediate ADCC are natural killer (NK) cells. The ability of NK cells to be activated in an antibody-dependent manner is reliant upon several factors. In general, NK cell-mediated antibody-dependent activation is most robust in terminally differentiated CD57(+) NK cells, as well as NK cells educated through ontological interactions between inhibitory killer immunoglobulin-like receptors (KIR) and their major histocompatibility complex class I [MHC-I or human leucocyte antigen (HLA-I)] ligands. With regard to anti-HIV-1 antibody-dependent NK cell activation, previous research has demonstrated that the epidemiologically relevant KIR3DL1/HLA-Bw4 receptor/ligand combination confers enhanced activation potential. In the present study we assessed the ability of the KIR2DL1/HLA-C2 receptor/ligand combination to confer enhanced activation upon direct stimulation with HLA-I-devoid target cells or antibody-dependent stimulation with HIV-1 gp140-pulsed CEM.NKr-CCR5 target cells in the presence of an anti-HIV-1 antibody source. Among donors carrying the HLA-C2 ligand for KIR2DL1, higher interferon (IFN)-γ production was observed within KIR2DL1(+) NK cells than in KIR2DL1(-) NK cells upon both direct and antibody-dependent stimulation. No differences in KIR2DL1(+) and KIR2DL1(-) NK cell activation were observed in HLA-C1 homozygous donors. Additionally, higher activation in KIR2DL1(+) than KIR2DL1(-) NK cells from HLA-C2 carrying donors was observed within less differentiated CD57(-) NK cells, demonstrating that the observed differences were due to education and not an overabundance of KIR2DL1(+) NK cells within differentiated CD57(+) NK cells. These observations are relevant for understanding the regulation of anti-HIV-1 antibody-dependent NK cell responses.
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: S L
authors.initials: SL
authors.lastname: Gooneratne
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, VIC, Australia.
authors.forename: R J
authors.initials: RJ
authors.lastname: Center
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia.|Melbourne Sexual Health Centre, Carlton, VIC, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Kent
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: M S
authors.initials: MS
authors.lastname: Parsons
mesh_terms: D000483:Alleles; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018959:CD57 Antigens / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D015236:HLA-C Antigens / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D056724:Immunity, Humoral; D007156:Immunologic Memory / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000187:drug effects; D061251:Primary Cell Culture; D054342:Receptors, KIR2DL1 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
chemical_list: D018959:CD57 Antigens; D015483:HIV Antibodies; D015236:HLA-C Antigens; C093100:KIR2DL1 protein, human; D054342:Receptors, KIR2DL1; D011994:Recombinant Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; D007371:Interferon-gamma
keywords: AIDS; killer immunoglobulin-like receptors; natural killer cells