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PMID: 16366734 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Activation of NK cells by an endocytosed receptor for soluble HLA-G.

PLoS biology ·Vol. 4 ·No. 1 ·2006-01-00 ·Pages e9

Rajagopalan S, Bryceson YT, Kuppusamy SP, Geraghty DE, van der Meer A, Joosten I, Long EO

Abstract

Signaling from endosomes is emerging as a mechanism by which selected receptors provide sustained signals distinct from those generated at the plasma membrane. The activity of natural killer (NK) cells, which are important effectors of innate immunity and regulators of adaptive immunity, is controlled primarily by receptors that are at the cell surface. Here we show that cytokine secretion by resting human NK cells is induced by soluble, but not solid-phase, antibodies to the killer cell immunoglobulin-like receptor (KIR) 2DL4, a receptor for human leukocyte antigen (HLA)-G. KIR2DL4 was constitutively internalized into Rab5-positive compartments via a dynamin-dependent process. Soluble HLA-G was endocytosed into KIR2DL4-containing compartments in NK cells and in 293T cells transfected with KIR2DL4. Chemokine secretion induced by KIR2DL4 transfection into 293T cells occurred only with recombinant forms of KIR2DL4 that trafficked to endosomes. The profile of genes up-regulated by KIR2DL4 engagement on resting NK cells revealed a proinflammatory/proangiogenic response. Soluble HLA-G induced secretion of a similar set of cytokines and chemokines. This unique stimulation of resting NK cells by soluble HLA-G, which is endocytosed by KIR2DL4, implies that NK cells may provide useful functions at sites of HLA-G expression, such as promotion of vascularization in maternal decidua during early pregnancy.

MeSH Terms
Chemokines/biosynthesis Cytokines/biosynthesis Dynamins/pharmacology Endocytosis/physiology Humans Interleukin-8/metabolism Killer Cells, Natural/drug effects,physiology Molecular Sequence Data Receptors, Immunologic/physiology Receptors, KIR Receptors, KIR2DL4 Receptors, KIR2DL5 Solubility Up-Regulation rab5 GTP-Binding Proteins/physiology
Chemicals
Chemokines Cytokines Interleukin-8 KIR2DL4 protein, human Receptors, Immunologic Receptors, KIR Receptors, KIR2DL4 Receptors, KIR2DL5 rab5 GTP-Binding Proteins Dynamins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Rajagopalan Sumati
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
Bryceson Yenan T
Kuppusamy Shanmuga P
Geraghty Daniel E
van der Meer Arnold
Joosten Irma
Long Eric O
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Article Info
Journal
PLoS biology
Abbr.
PLoS Biol
ISSN
1545-7885
DOI
10.1371/journal.pbio.0040009
Published
2006-01-00
Pages
e9
Language
English
Region
United States
NLM ID
101183755
PMCID
PMC1318474
Subset
IM
Grants
Intramural NIH HHS · United States
Databases
GENBANK
DQ266438, M90683
External Links
PubMed source DOI: 10.1371/journal.pbio.0040009 PMC Full Text View journal details
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