title: The role of natural killer (NK) cells and NK cell receptor polymorphisms in the assessment of HIV-1 neutralization.
abstract: The importance of innate immune cells in HIV-1 pathogenesis and protection has been highlighted by the role of natural killer (NK) cells in the containment of viral replication. Use of peripheral blood mononuclear cells (PBMC) in immunologic studies provides both HIV-1 target cells (ie. CD4+ T cells), as well as anti-HIV-1 effector cells, such as NK cells. In this study, NK and other immune cell populations were analyzed in HIV-negative donor PBMC for an impact on the anti-HIV activity of polyclonal and monoclonal antibodies. NK cell percentages were significantly higher in donor PBMC that supported lower levels of viral replication. While the percentage of NK cells was not directly associated with neutralization titers, NK cell-depletion significantly diminished the antiviral antibody activity by up to three logs, and polymorphisms in NK killer immunoglobulin receptor (KIR) and FcγRIIIa alleles appear to be associated with this affect. These findings demonstrate that NK cells and NK cell receptor polymorphisms may influence assessment of traditional HIV-1 neutralization in a platform where antibody is continuously present. This format appears to simultaneously assess conventional entry inhibition (neutralization) and non-neutralizing antibody-dependent HIV inhibition, which may provide the opportunity to delineate the dominant antibody function(s) in polyclonal vaccine responses.
authors.affiliation: Military HIV Research Program (MHRP), Rockville, Maryland, United States of America.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Brown
authors.forename: Lindsay
authors.initials: L
authors.lastname: Wieczorek
authors.forename: Gustavo
authors.initials: G
authors.lastname: Kijak
authors.forename: Kara
authors.initials: K
authors.lastname: Lombardi
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Currier
authors.forename: Maggie
authors.initials: M
authors.lastname: Wesberry
authors.forename: John C
authors.initials: JC
authors.lastname: Kappes
authors.forename: Viseth
authors.initials: V
authors.lastname: Ngauy
authors.forename: Mary
authors.initials: M
authors.lastname: Marovich
authors.forename: Nelson
authors.initials: N
authors.lastname: Michael
authors.forename: Christina
authors.initials: C
authors.lastname: Ochsenbauer
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Polonis
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D005838:Genotype; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D009500:Neutralization Tests; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics; D054349:Receptors, KIR3DS1 / Q000235:genetics; D055607:Receptors, Natural Killer Cell / Q000235:genetics*
chemical_list: D057134:Antibodies, Neutralizing; C496124:FCGR3A protein, human; D017452:Receptors, IgG; D054349:Receptors, KIR3DS1; D055607:Receptors, Natural Killer Cell