KIR2DL4 (CD158d): An activation receptor for HLA-G

KIR2DL4 is an unusual killer cell immunoglobulin-like receptor (KIR) family member in terms of its structure, expression, cellular localization, and signaling properties. The most conserved KIR in evolution, it is referred to as a framework KIR gene and is expressed by all natural killer (NK) cells...

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Main Authors:	Rajagopalan, Sumati, Long, Eric O.
Format:	Online
Language:	English
Published:	Frontiers Research Foundation 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422731/

id	pubmed-3422731
recordtype	oai_dc
spelling	pubmed-34227312012-08-29 KIR2DL4 (CD158d): An activation receptor for HLA-G Rajagopalan, Sumati Long, Eric O. Immunology KIR2DL4 is an unusual killer cell immunoglobulin-like receptor (KIR) family member in terms of its structure, expression, cellular localization, and signaling properties. The most conserved KIR in evolution, it is referred to as a framework KIR gene and is expressed by all natural killer (NK) cells and a subset of T cells. Although it has a long cytoplasmic tail that is typical of inhibitory KIR, engagement of this receptor results in the activation of NK cells, not for cytotoxicity, but for cytokine and chemokine secretion. Unlike all other KIRs, which are expressed on the surface of NK cells, KIR2DL4 resides in endosomes. It signals from this intracellular site for a proinflammatory and proangiogenic response, using a novel endosomal signaling pathway that involves the serine/threonine kinases DNA-PKcs and Akt. The only known ligand of KIR2DL4 is HLA-G. Soluble HLA-G accumulates in KIR2DL4+ endosomes. Unlike classical HLA molecules that serve as ligands for other KIR family members, in healthy individuals, HLA-G expression is restricted to the fetal trophoblast cells that invade the maternal decidua during early pregnancy. Since NK cells constitute the predominant lymphocyte subset at this site, the proinflammatory/proangiogenic outcome of the interaction between KIR2DL4 and soluble HLA-G supports a role for KIR2DL4 in the extensive remodeling of the maternal vasculature during the early weeks of pregnancy. Frontiers Research Foundation 2012-08-20 /pmc/articles/PMC3422731/ /pubmed/22934097 http://dx.doi.org/10.3389/fimmu.2012.00258 Text en Copyright © Rajagopalan and Long. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
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	Rajagopalan, Sumati Long, Eric O.
spellingShingle	Rajagopalan, Sumati Long, Eric O. KIR2DL4 (CD158d): An activation receptor for HLA-G
author_facet	Rajagopalan, Sumati Long, Eric O.
author_sort	Rajagopalan, Sumati
title	KIR2DL4 (CD158d): An activation receptor for HLA-G
title_short	KIR2DL4 (CD158d): An activation receptor for HLA-G
title_full	KIR2DL4 (CD158d): An activation receptor for HLA-G
title_fullStr	KIR2DL4 (CD158d): An activation receptor for HLA-G
title_full_unstemmed	KIR2DL4 (CD158d): An activation receptor for HLA-G
title_sort	kir2dl4 (cd158d): an activation receptor for hla-g
description	KIR2DL4 is an unusual killer cell immunoglobulin-like receptor (KIR) family member in terms of its structure, expression, cellular localization, and signaling properties. The most conserved KIR in evolution, it is referred to as a framework KIR gene and is expressed by all natural killer (NK) cells and a subset of T cells. Although it has a long cytoplasmic tail that is typical of inhibitory KIR, engagement of this receptor results in the activation of NK cells, not for cytotoxicity, but for cytokine and chemokine secretion. Unlike all other KIRs, which are expressed on the surface of NK cells, KIR2DL4 resides in endosomes. It signals from this intracellular site for a proinflammatory and proangiogenic response, using a novel endosomal signaling pathway that involves the serine/threonine kinases DNA-PKcs and Akt. The only known ligand of KIR2DL4 is HLA-G. Soluble HLA-G accumulates in KIR2DL4+ endosomes. Unlike classical HLA molecules that serve as ligands for other KIR family members, in healthy individuals, HLA-G expression is restricted to the fetal trophoblast cells that invade the maternal decidua during early pregnancy. Since NK cells constitute the predominant lymphocyte subset at this site, the proinflammatory/proangiogenic outcome of the interaction between KIR2DL4 and soluble HLA-G supports a role for KIR2DL4 in the extensive remodeling of the maternal vasculature during the early weeks of pregnancy.
publisher	Frontiers Research Foundation
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422731/
_version_	1611550654200807424

KIR2DL4 (CD158d): An activation receptor for HLA-G

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