Suppression of a Natural Killer Cell Response by Simian Immunodeficiency Virus Peptides

Suppression of a Natural Killer Cell Response by Simian Immunodeficiency Virus Peptides

Natural killer (NK) cell responses in primates are regulated in part through interactions between two highly polymorphic molecules, the killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their major histocompatibility complex (MHC) class I ligands on target cells. We previously reporte...

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Main Authors: Schafer, Jamie L., Ries, Moritz, Guha, Natasha, Connole, Michelle, Colantonio, Arnaud D., Wiertz, Emmanuel J., Wilson, Nancy A., Kaur, Amitinder, Evans, David T.
Format: Online
Language:English
Published: Public Library of Science 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557930/
id pubmed-4557930
recordtype oai_dc
spelling pubmed-45579302015-09-10 Suppression of a Natural Killer Cell Response by Simian Immunodeficiency Virus Peptides Schafer, Jamie L. Ries, Moritz Guha, Natasha Connole, Michelle Colantonio, Arnaud D. Wiertz, Emmanuel J. Wilson, Nancy A. Kaur, Amitinder Evans, David T. Research Article Natural killer (NK) cell responses in primates are regulated in part through interactions between two highly polymorphic molecules, the killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their major histocompatibility complex (MHC) class I ligands on target cells. We previously reported that the binding of a common MHC class I molecule in the rhesus macaque, Mamu-A1*002, to the inhibitory receptor Mamu-KIR3DL05 is stabilized by certain simian immunodeficiency virus (SIV) peptides, but not by others. Here we investigated the functional implications of these interactions by testing SIV peptides bound by Mamu-A1*002 for the ability to modulate Mamu-KIR3DL05+ NK cell responses. Twenty-eight of 75 SIV peptides bound by Mamu-A1*002 suppressed the cytolytic activity of primary Mamu-KIR3DL05+ NK cells, including three immunodominant CD8+ T cell epitopes previously shown to stabilize Mamu-A1*002 tetramer binding to Mamu-KIR3DL05. Substitutions at C-terminal positions changed inhibitory peptides into disinhibitory peptides, and vice versa, without altering binding to Mamu-A1*002. The functional effects of these peptide variants on NK cell responses also corresponded to their effects on Mamu-A1*002 tetramer binding to Mamu-KIR3DL05. In assays with mixtures of inhibitory and disinhibitory peptides, low concentrations of inhibitory peptides dominated to suppress NK cell responses. Consistent with the inhibition of Mamu-KIR3DL05+ NK cells by viral epitopes presented by Mamu-A1*002, SIV replication was significantly higher in Mamu-A1*002+ CD4+ lymphocytes co-cultured with Mamu-KIR3DL05+ NK cells than with Mamu-KIR3DL05- NK cells. These results demonstrate that viral peptides can differentially affect NK cell responses by modulating MHC class I interactions with inhibitory KIRs, and provide a mechanism by which immunodeficiency viruses may evade NK cell responses. Public Library of Science 2015-09-02 /pmc/articles/PMC4557930/ /pubmed/26333068 http://dx.doi.org/10.1371/journal.ppat.1005145 Text en © 2015 Schafer et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Schafer, Jamie L.
Ries, Moritz
Guha, Natasha
Connole, Michelle
Colantonio, Arnaud D.
Wiertz, Emmanuel J.
Wilson, Nancy A.
Kaur, Amitinder
Evans, David T.
spellingShingle Schafer, Jamie L.
Ries, Moritz
Guha, Natasha
Connole, Michelle
Colantonio, Arnaud D.
Wiertz, Emmanuel J.
Wilson, Nancy A.
Kaur, Amitinder
Evans, David T.
Suppression of a Natural Killer Cell Response by Simian Immunodeficiency Virus Peptides
author_facet Schafer, Jamie L.
Ries, Moritz
Guha, Natasha
Connole, Michelle
Colantonio, Arnaud D.
Wiertz, Emmanuel J.
Wilson, Nancy A.
Kaur, Amitinder
Evans, David T.
author_sort Schafer, Jamie L.
title Suppression of a Natural Killer Cell Response by Simian Immunodeficiency Virus Peptides
title_short Suppression of a Natural Killer Cell Response by Simian Immunodeficiency Virus Peptides
title_full Suppression of a Natural Killer Cell Response by Simian Immunodeficiency Virus Peptides
title_fullStr Suppression of a Natural Killer Cell Response by Simian Immunodeficiency Virus Peptides
title_full_unstemmed Suppression of a Natural Killer Cell Response by Simian Immunodeficiency Virus Peptides
title_sort suppression of a natural killer cell response by simian immunodeficiency virus peptides
description Natural killer (NK) cell responses in primates are regulated in part through interactions between two highly polymorphic molecules, the killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their major histocompatibility complex (MHC) class I ligands on target cells. We previously reported that the binding of a common MHC class I molecule in the rhesus macaque, Mamu-A1*002, to the inhibitory receptor Mamu-KIR3DL05 is stabilized by certain simian immunodeficiency virus (SIV) peptides, but not by others. Here we investigated the functional implications of these interactions by testing SIV peptides bound by Mamu-A1*002 for the ability to modulate Mamu-KIR3DL05+ NK cell responses. Twenty-eight of 75 SIV peptides bound by Mamu-A1*002 suppressed the cytolytic activity of primary Mamu-KIR3DL05+ NK cells, including three immunodominant CD8+ T cell epitopes previously shown to stabilize Mamu-A1*002 tetramer binding to Mamu-KIR3DL05. Substitutions at C-terminal positions changed inhibitory peptides into disinhibitory peptides, and vice versa, without altering binding to Mamu-A1*002. The functional effects of these peptide variants on NK cell responses also corresponded to their effects on Mamu-A1*002 tetramer binding to Mamu-KIR3DL05. In assays with mixtures of inhibitory and disinhibitory peptides, low concentrations of inhibitory peptides dominated to suppress NK cell responses. Consistent with the inhibition of Mamu-KIR3DL05+ NK cells by viral epitopes presented by Mamu-A1*002, SIV replication was significantly higher in Mamu-A1*002+ CD4+ lymphocytes co-cultured with Mamu-KIR3DL05+ NK cells than with Mamu-KIR3DL05- NK cells. These results demonstrate that viral peptides can differentially affect NK cell responses by modulating MHC class I interactions with inhibitory KIRs, and provide a mechanism by which immunodeficiency viruses may evade NK cell responses.
publisher Public Library of Science
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557930/
_version_ 1613472026762149888

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