title: NKG2D Acts as a Co-Receptor for Natural Killer Cell-Mediated Anti-HIV-1 Antibody-Dependent Cellular Cytotoxicity.
abstract: The utility of antibody-dependent cellular cytotoxicity (ADCC) for eliminating HIV-1-infected cells is of much interest for the design of both prophylactic vaccines for HIV-1 prevention and therapeutics to eliminate latently infected cells following reactivation. Significant research has been conducted to understand the antibody specificities involved in anti-HIV-1 ADCC responses. Perhaps equally important as the identity of the antibodies mediating these responses are factors regulating the ability of ADCC effector cells, in particular, natural killer (NK) cells, to respond to antibody-coated target cells. Indeed, a plethora of activating and inhibitory receptors expressed on the surface of NK cells might act in conjunction with CD16 to influence ADCC. As the expression of NKG2D and its ligands has been linked to HIV-1 disease progression, we evaluated if signals through NKG2D were involved in anti-HIV-1 ADCC. Utilizing assays measuring cytolysis, we provide the first data implicating NKG2D in antibody-dependent NK cell responses against a target cell line either pulsed with gp120 or infected with HIV-1. These observations are highly significant for understanding antibody-dependent NK cell responses against HIV-1 and might be useful for optimizing prophylactics and therapeutics aiming to utilize antibodies and optimally functional NK cells to control HIV-1.
authors.affiliation: 1 Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Australia .
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Parsons
authors.affiliation: 2 Department of Microbiology, Infectiology and Immunology, Centre de Recherche du CHUM, Université de Montreal , Montreal, Canada .
authors.forename: Jonathan
authors.initials: J
authors.lastname: Richard
authors.affiliation: 1 Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Australia .
authors.forename: Wen Shi
authors.initials: WS
authors.lastname: Lee
authors.affiliation: 1 Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Australia .
authors.forename: Hillary
authors.initials: H
authors.lastname: Vanderven
authors.affiliation: 3 Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland , St. John's, Canada .
authors.forename: Michael D
authors.initials: MD
authors.lastname: Grant
authors.affiliation: 2 Department of Microbiology, Infectiology and Immunology, Centre de Recherche du CHUM, Université de Montreal , Montreal, Canada .
authors.forename: Andrés
authors.initials: A
authors.lastname: Finzi
authors.affiliation: 1 Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Australia .|4 Melbourne Sexual Health Centre, Central Clinical School, Monash University , Melbourne, Australia .|5 ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne , Parkville, Australia .
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity; D003601:Cytotoxicity Tests, Immunologic; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011956:Receptors, Cell Surface
keywords: ADCC; NK cells; NKG2D