Inhibitory Killer Immunoglobulin-like receptors to self HLA-B and HLA-C ligands contribute differentially to Natural Killer cell functional potential in HIV infected slow progressors

Kamya, Philomena; Tallon, B; Melendez-Peña, Carlos E; Parsons, Matthew S.; Migueles, Stephen A.; Connors, Mark; Miconiatis, S; Song, Rujun; Boulet, Salix; Bruneau, Julie; Tremblay, Cécile; Bernard, Nicole F.

doi:10.1016/j.clim.2012.01.001

Cited by 14 publications

(8 citation statements)

References 32 publications

(29 reference statements)

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“…Previous reports have studied NK‐cell licensing in HIV‐1 infection, predominantly analyzing individuals with the protective KIR3DL1 + /HLA‐Bw4 + haplotypes. In most of these, NK cells derived from slow progressors or viremic controllers display a licensed phenotype in comparison to NK cells obtained from HLA‐Bw6 + individuals . However, functional impairment of licensed NK cells including antibody‐dependent cell‐mediated cytotoxicity and decreased frequency of polyfunctional NK cells in subjects with chronic HIV‐1 infection have been reported .…”

Section: Discussionmentioning

confidence: 99%

Increased frequency and function of KIR2DL1–3⁺ NK cells in primary HIV‐1 infection are determined by HLA‐C group haplotypes

et al. 2014

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Acquisition and maintenance of NK cell function is mediated by inhibitory killer-cell immunoglobulin-like receptors (KIR) through the interaction with HLA class I molecules. Recently, HLA-C expression levels were shown to be correlated with protection against multiple outcomes of HIV-1 infection; however the underlying mechanisms are poorly understood. As HLA-C is the natural ligand for the inhibitory receptors KIR2DL1 and KIR2DL2/3, we sought to determine whether HLA-C group haplotypes affect NK cell responses during primary HIV-1 infection. The phenotypes and functional capacity of NK cells derived from HIV-1(+) and HIV-1(-) individuals were assessed (N=42 and N=40, respectively). HIV-1 infection was associated with an increased frequency of KIR2DL1-3+ NK cells. Further analysis showed that KIR2DL1+ NK cells were selectively increased in individuals homozygous for HLA-C2, while HLA-C1-homozygous individuals displayed increased proportions of KIR2DL2/3+ NK cells. KIR2DL1-3+ NK cells were furthermore more polyfunctional during primary HIV-1 infection in individuals also encoding for their cognate HLA-C group haplotypes as measured by degranulation and cytokine production. These results identify a novel relationship between HLA-C and KIR2DL+ NK cell subsets and demonstrate that HLA-C-mediated licensing modulates NK cell responses to primary HIV-1 infection.

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Section: Discussionmentioning

confidence: 99%

Increased frequency and function of KIR2DL1–3⁺ NK cells in primary HIV‐1 infection are determined by HLA‐C group haplotypes

et al. 2014

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“…While this study evaluated the anti-HIV ADCC activity of NK cells educated through the epidemiologically interesting 3DL1/HLA-Bw4 interactions (22), future research should investigate the impact of other HLA/KIR combinations and the cumulative HLA/KIR phenotype of NK cells on the ability of NK cells to mediate autologous anti-HIV ADCC. Interestingly, Kamya et al recently showed that while HLA-Bw4/KIR3DL1 combinations contribute to the ability of NK cells to be activated by K562 cells devoid of HLA, HLA-C/KIR2DL1/2/3 combinations did not contribute to the ability of NK cells to be activated by this stimulation (17). In contrast, both HLA-Bw4/KIR3DL1 and HLA-C/KIR2DL1/2/3 combinations contributed to the ability of NK cells from healthy controls to be activated by K562 stimulation.…”

Section: Discussionmentioning

confidence: 99%

HIV Infection Abrogates the Functional Advantage of Natural Killer Cells Educated through KIR3DL1/HLA-Bw4 Interactions To Mediate Anti-HIV Antibody-Dependent Cellular Cytotoxicity

Parsons

Wren

Isitman

et al. 2012

J Virol

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“…Individuals with multiple copies of KIR3DL1 in the presence of KIR3DS1 may harbor an expanded pool of KIR3DS1 + cells, which could contribute to greater antiviral activity upon infection. Another study reported stronger NK cell responses to HLA deficient K562 cells among HIV infected slow progressor individuals with KIR3DL1 and HLA-Bw4 as compared to individuals without this receptor/ligand combination (181), further supporting a contribution of an NK cell licensing effect. All individuals in this study were homozygous for KIR3DL1 .…”

Section: The Kir3dl1/s1 Locus In Hiv/aidsmentioning

confidence: 93%

Immunogenetics of HIV disease

Martin

Carrington

2013

Immunological Reviews

136

133

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Summary Host genetic factors are a major contributing factor to the inter-individual variation observed in response to human immunodeficiency virus (HIV) infection and are linked to resistance to HIV infection among exposed individuals, as well as rate of disease progression and the likelihood of viral transmission. Of the genetic variants that have been shown to affect the natural history of HIV infection, the human leukocyte antigen (HLA) class I genes exhibit the strongest and most consistent association, underscoring a central role for CD8+ T cells in resistance to the virus. HLA proteins play important roles in T-cell-mediated adaptive immunity by presenting immunodominant HIV epitopes to cytotoxic T lymphocytes (CTLs) and CD4+ T cells. Genetic and functional data also indicate a function for HLA in natural killer (NK) cell-mediated innate immunity against HIV by interacting with killer cell immunoglobulin-like receptors (KIR). We review the HLA and KIR associations with HIV disease and discuss the mechanisms underlying these associations.

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Inhibitory Killer Immunoglobulin-like receptors to self HLA-B and HLA-C ligands contribute differentially to Natural Killer cell functional potential in HIV infected slow progressors

Abstract: word count: 151 Manuscript word count: 3,742 1

Cited by 14 publications

References 32 publications

Increased frequency and function of KIR2DL1–3⁺ NK cells in primary HIV‐1 infection are determined by HLA‐C group haplotypes

Increased frequency and function of KIR2DL1–3⁺ NK cells in primary HIV‐1 infection are determined by HLA‐C group haplotypes

HIV Infection Abrogates the Functional Advantage of Natural Killer Cells Educated through KIR3DL1/HLA-Bw4 Interactions To Mediate Anti-HIV Antibody-Dependent Cellular Cytotoxicity

Immunogenetics of HIV disease

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Inhibitory Killer Immunoglobulin-like receptors to self HLA-B and HLA-C ligands contribute differentially to Natural Killer cell functional potential in HIV infected slow progressors

Abstract: word count: 151 Manuscript word count: 3,742 1

Cited by 14 publications

References 32 publications

Increased frequency and function of KIR2DL1–3+ NK cells in primary HIV‐1 infection are determined by HLA‐C group haplotypes

Increased frequency and function of KIR2DL1–3+ NK cells in primary HIV‐1 infection are determined by HLA‐C group haplotypes

HIV Infection Abrogates the Functional Advantage of Natural Killer Cells Educated through KIR3DL1/HLA-Bw4 Interactions To Mediate Anti-HIV Antibody-Dependent Cellular Cytotoxicity

Immunogenetics of HIV disease

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Increased frequency and function of KIR2DL1–3⁺ NK cells in primary HIV‐1 infection are determined by HLA‐C group haplotypes

Increased frequency and function of KIR2DL1–3⁺ NK cells in primary HIV‐1 infection are determined by HLA‐C group haplotypes