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@article{ab68d5356b2d4ff3ac917b5e43afe409,
title = "Impact of the variable killer Ig-like receptor-human leukocyte antigen interactions on natural killer cell cytotoxicity toward foreign CD4 T cells",
abstract = "Background: Natural killer (NK) cells are known to mount a response against foreign target cells, where the absence of the dominant inhibitory killer Ig-like receptor (KIR)-human leukocyte antigen (HLA) interaction immensely lowers the threshold for NK cell activation. NK cells could thus constitute a vital part in the mucosal defense against cell-associated sexually transmitted diseases. Here, we performed a detailed analysis of hitherto unexplored KIR-HLA-incompatible NK cell interactions.Methods and findings: In vitro, healthy NK cells were cocultured with CD4+ T cells derived from human immunodeficiency virus-1 patients, and the KIR-specific NK cell cytotoxicity was measured using flow cytometry. Genotyping of KIR and HLA predicted the KIR-HLA interactions occurring during these 124 allogeneic encounters. KIR2DL1+ NK cells were seen as the strongest intrinsic responders in the absence of their ligand with a 3.2-fold increase in KIR2DL1+ NK cells in the total NK cell response. An association between the size of the alloreactive NK cell population and the amount of CD4+ T cell death (p = 0.0023) and NK cell degranulation (p = 0.0036) was only present in NK cell donors with an activating KIR haplotype.conclusion: We demonstrate differences in the activating effect of KIR-HLA incompatibility according to the KIR involved, with KIR2DL1 as the strongest responder. An activating KIR haplotype optimized the contribution of KIR-HLA-incompatible NK cells in the total NK cell response.",
keywords = "allogeneic natural killer cell responses, killer Ig-like receptor-human leukocyte antigen ligand mismatch, in vitro natural killer-CD4 cocultures, human immunodeficiency virus-1 patients, HIV transmission, MHC CLASS-I, IMMUNOGLOBULIN-LIKE RECEPTORS, HUMAN NK CELLS, INHIBITORY RECEPTORS, SURFACE-MOLECULE, ACUTE-LEUKEMIA, COMPLEX, HLA, RECOGNITION, RESPONSIVENESS",
author = "Jef Hens and Odin Goovaerts and Ann Ceulemans and Wim Jennes and Luc Kestens",
note = "FTX",
year = "2018",
doi = "10.3389/fimmu.2018.01588",
language = "English",
volume = "9",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",

}

RIS

TY - JOUR

T1 - Impact of the variable killer Ig-like receptor-human leukocyte antigen interactions on natural killer cell cytotoxicity toward foreign CD4 T cells

AU - Hens, Jef

AU - Goovaerts, Odin

AU - Ceulemans, Ann

AU - Jennes, Wim

AU - Kestens, Luc

N1 - FTX

PY - 2018

Y1 - 2018

N2 - Background: Natural killer (NK) cells are known to mount a response against foreign target cells, where the absence of the dominant inhibitory killer Ig-like receptor (KIR)-human leukocyte antigen (HLA) interaction immensely lowers the threshold for NK cell activation. NK cells could thus constitute a vital part in the mucosal defense against cell-associated sexually transmitted diseases. Here, we performed a detailed analysis of hitherto unexplored KIR-HLA-incompatible NK cell interactions.Methods and findings: In vitro, healthy NK cells were cocultured with CD4+ T cells derived from human immunodeficiency virus-1 patients, and the KIR-specific NK cell cytotoxicity was measured using flow cytometry. Genotyping of KIR and HLA predicted the KIR-HLA interactions occurring during these 124 allogeneic encounters. KIR2DL1+ NK cells were seen as the strongest intrinsic responders in the absence of their ligand with a 3.2-fold increase in KIR2DL1+ NK cells in the total NK cell response. An association between the size of the alloreactive NK cell population and the amount of CD4+ T cell death (p = 0.0023) and NK cell degranulation (p = 0.0036) was only present in NK cell donors with an activating KIR haplotype.conclusion: We demonstrate differences in the activating effect of KIR-HLA incompatibility according to the KIR involved, with KIR2DL1 as the strongest responder. An activating KIR haplotype optimized the contribution of KIR-HLA-incompatible NK cells in the total NK cell response.

AB - Background: Natural killer (NK) cells are known to mount a response against foreign target cells, where the absence of the dominant inhibitory killer Ig-like receptor (KIR)-human leukocyte antigen (HLA) interaction immensely lowers the threshold for NK cell activation. NK cells could thus constitute a vital part in the mucosal defense against cell-associated sexually transmitted diseases. Here, we performed a detailed analysis of hitherto unexplored KIR-HLA-incompatible NK cell interactions.Methods and findings: In vitro, healthy NK cells were cocultured with CD4+ T cells derived from human immunodeficiency virus-1 patients, and the KIR-specific NK cell cytotoxicity was measured using flow cytometry. Genotyping of KIR and HLA predicted the KIR-HLA interactions occurring during these 124 allogeneic encounters. KIR2DL1+ NK cells were seen as the strongest intrinsic responders in the absence of their ligand with a 3.2-fold increase in KIR2DL1+ NK cells in the total NK cell response. An association between the size of the alloreactive NK cell population and the amount of CD4+ T cell death (p = 0.0023) and NK cell degranulation (p = 0.0036) was only present in NK cell donors with an activating KIR haplotype.conclusion: We demonstrate differences in the activating effect of KIR-HLA incompatibility according to the KIR involved, with KIR2DL1 as the strongest responder. An activating KIR haplotype optimized the contribution of KIR-HLA-incompatible NK cells in the total NK cell response.

KW - allogeneic natural killer cell responses

KW - killer Ig-like receptor-human leukocyte antigen ligand mismatch

KW - in vitro natural killer-CD4 cocultures

KW - human immunodeficiency virus-1 patients

KW - HIV transmission

KW - MHC CLASS-I

KW - IMMUNOGLOBULIN-LIKE RECEPTORS

KW - HUMAN NK CELLS

KW - INHIBITORY RECEPTORS

KW - SURFACE-MOLECULE

KW - ACUTE-LEUKEMIA

KW - COMPLEX

KW - HLA

KW - RECOGNITION

KW - RESPONSIVENESS

U2 - 10.3389/fimmu.2018.01588

DO - 10.3389/fimmu.2018.01588

M3 - A1: Web of Science-article

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 1588

ER -

ID: 2611969