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

PLoS Pathogens
Jamie L SchaferDavid T Evans

Abstract

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-K...Continue Reading

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Citations

Nov 23, 2015·Current Opinion in Virology·Stephen N WaggonerCarolyn E Rydyznski
Sep 21, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Priyankana BanerjeeDavid T Evans
May 7, 2016·Current Opinion in HIV and AIDS·Nitasha KumarGuido Silvestri
Aug 18, 2016·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Kim L WeisgrauEva G Rakasz
Jul 12, 2017·Immunogenetics·Paola Carrillo-BustamanteCan Keşmir

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Methods Mentioned

BETA
flow cytometry
ELISA
sedation
FACS
Assay

Software Mentioned

UCSF Chimera package
FlowJo

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