title: Frequent and strong antibody-mediated natural killer cell activation in response to HIV-1 Env in individuals with chronic HIV-1 infection.
abstract: Natural killer (NK) cells play a critical role in the control of HIV-1 infection, and NK cells that respond to HIV-1 peptides have been recently described. However, the mechanisms by which NK cells recognize HIV-1 antigens are not fully understood. We investigated NK cell activation in response to HIV-1 peptides during early and chronic HIV-1 clade B infection using a whole-blood assay and multiparameter flow cytometry. Antibody-mediated NK cell activation in response to HIV-1 peptides was not detected in HIV-1-uninfected individuals. In contrast, 79% of individuals with chronic infection and 22% of individuals with early infection had detectable gamma interferon (IFN-γ) NK cell responses to HIV-1 antigens (P < 0.00001). IFN-γ- and tumor necrosis factor alpha (TNF-α)-producing NK cells most frequently targeted Env gp120 (median of 4% and range of 0 to 31% of all NK cells). NK cells rarely targeted other HIV-1 proteins such as Gag, Pol, and Nef. Antibody-mediated NK cell responses to peptides mapped predominantly to Env protein, required the presence of plasma or plasma IgG, and resulted in lower CD16 expression on NK cells, suggesting an antibody-mediated activation of NK cells. Further studies are needed to assess the consequences of these antibody-mediated NK cell responses for HIV-1 disease progression and vaccine-induced protection from infection.
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Christina F
authors.initials: CF
authors.lastname: Thobakgale
authors.forename: Lena
authors.initials: L
authors.lastname: Fadda
authors.forename: Kimberly
authors.initials: K
authors.lastname: Lane
authors.forename: Ildiko
authors.initials: I
authors.lastname: Toth
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
authors.forename: Suzane
authors.initials: S
authors.lastname: Bazner
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology*; D002908:Chronic Disease; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male
chemical_list: D000914:Antibodies, Viral; D015699:HIV Envelope Protein gp120; C573415:IFNG protein, human; D007074:Immunoglobulin G; D007371:Interferon-gamma