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Spatial Clustering of Receptors and Signaling Molecules Regulates NK Cell Response to Peptide Repertoire Changes.


ABSTRACT: Natural Killer (NK) cell activation requires integration of inhibitory and activating signaling. Inhibitory signals are determined by members of the killer cell immunoglobulin-like receptor (KIR) family, which have major histocompatibility complex (MHC) class I ligands. Loss of this inhibitory signal leads to NK cell activation. Thus, down-regulation of MHC I during viral infection or cancer induces NK cell activation. However, NK cell activation in the presence of MHC-I has been demonstrated for HLA-C*0102 through changes in its peptide content: "peptide antagonism." Here we identify an antagonist peptide for HLA-C*0304 suggesting that peptide antagonism is a generalizable phenomenon and, using a combination of mathematical modeling, confocal imaging, and immune-assays, we quantitatively determine mechanisms that underlie peptide antagonism in inhibitory KIR2DL2/3 signaling. These data provide a mechanism for NK cell activation based on a reduction of inhibitory signaling in the presence of preserved levels of MHC class I.

SUBMITTER: Mbiribindi B 

PROVIDER: S-EPMC6460049 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Spatial Clustering of Receptors and Signaling Molecules Regulates NK Cell Response to Peptide Repertoire Changes.

Mbiribindi Berenice B   Mukherjee Sayak S   Wellington Dannielle D   Das Jayajit J   Khakoo Salim I SI  

Frontiers in immunology 20190405


Natural Killer (NK) cell activation requires integration of inhibitory and activating signaling. Inhibitory signals are determined by members of the killer cell immunoglobulin-like receptor (KIR) family, which have major histocompatibility complex (MHC) class I ligands. Loss of this inhibitory signal leads to NK cell activation. Thus, down-regulation of MHC I during viral infection or cancer induces NK cell activation. However, NK cell activation in the presence of MHC-I has been demonstrated fo  ...[more]

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