Expression of Ly49E and CD94/NKG2 on Fetal and Adult NK Cells

Beneden, Katrien Van; Stevenaert, Frederik; Creus, An De; Debacker, Veronique; Boever, J. De; Plum, Jean; Leclercq, Georges

doi:10.4049/jimmunol.166.7.4302

Cited by 59 publications

(78 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the available data suggest that the majority of Ly49 receptors expressed in B6 mice are specific for classical MHC-I molecules. No MHC-I ligand has been identified for the activating Ly49H, which binds to the MCMV m157 protein (27,28), and no ligand is known for Ly49E, which is predominantly expressed in fetal NK cells and certain TCR␥␦ T cells (17,29).…”

Section: Discussionmentioning

confidence: 99%

“…Ly49 cDNAs in eukaryotic expression vectors have been described before (15,17). Ly49B, C, G2, I, and Q were either subcloned directly or PCR amplified from plasmid DNA and B6 day 14 fetal liver cDNA, respectively, before cloning into a modified pEF-BOS internal ribosome entry site puro expression vector to introduce a NH 2 -terminal vesicular stomatitis virus (VSV) tag.…”

Section: Constructsmentioning

confidence: 99%

See 1 more Smart Citation

Interactions of Ly49 Family Receptors with MHC Class I Ligands in trans and cis

Scarpellino

Oeschger

Guillaume

et al. 2007

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

The Ly49A NK cell receptor interacts with MHC class I (MHC-I) molecules on target cells and negatively regulates NK cell-mediated target cell lysis. We have recently shown that the MHC-I ligand-binding capacity of the Ly49A NK cell receptor is controlled by the NK cells’ own MHC-I. To see whether this property was unique to Ly49A, we have investigated the binding of soluble MHC-I multimers to the Ly49 family receptors expressed in MHC-I-deficient and -sufficient C57BL/6 mice. In this study, we confirm the binding of classical MHC-I to the inhibitory Ly49A, C and I receptors, and demonstrate that detectable MHC-I binding to MHC-I-deficient NK cells is exclusively mediated by these three receptors. We did not detect significant multimer binding to stably transfected or NK cell-expressed Ly49D, E, F, G, and H receptors. Yet, we identified the more distantly related Ly49B and Ly49Q, which are not expressed by NK cells, as two novel MHC-I receptors in mice. Furthermore, we show using MHC-I-sufficient mice that the NK cells’ own MHC-I significantly masks the Ly49A and Ly49C, but not the Ly49I receptor. Nevertheless, Ly49I was partly masked on transfected tumor cells, suggesting that the structure of Ly49I is compatible in principal with cis binding of MHC-I. Finally, masking of Ly49Q by cis MHC-I was minor, whereas masking of Ly49B was not detected. These data significantly extend the MHC-I specificity of Ly49 family receptors and show that the accessibility of most, but not all, MHC-I-binding Ly49 receptors is modulated by the expression of MHC-I in cis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Constructsmentioning

confidence: 99%

Interactions of Ly49 Family Receptors with MHC Class I Ligands in trans and cis

Scarpellino

Oeschger

Guillaume

et al. 2007

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…4J and data not shown). We determined expression of Ly49C by staining with the anti-Ly49C/ Ly49E 4D12 antibody as adult NK cells only contain approximately 1% Ly49E 1 NK cells [32]. There was no difference in the expression of the inhibitory CD94/NKG2A and activating CD94/ NKG2(C-E) heterodimeric receptors ( Fig.…”

Section: Altered Nk Cell Phenotype In Cd70-tg Micementioning

confidence: 99%

Continuous CD27 triggering in vivo strongly reduces NK cell numbers

et al. 2010

Self Cite

View full text Add to dashboard Cite

NK cells are important mediators of the early defense. In mice, immature and mature NK (mNK) cells constitutively express the TNF receptor family member CD27; however, mNK cells eventually lose CD27 expression and become resting NK cells. Interaction of CD27 with its ligand, CD70, enhances proliferation and effector functions of NK cells. We used mice that constitutively express CD70 on B cells (CD70-Tg) to study the in vivo effects of continuous triggering of CD27 on NK cells. Continuous CD70-CD27 interaction resulted in strongly down-modulated CD27 expression on NK cells and gradually reduced absolute NK cell numbers. This reduction was most prominent in the mNK cell subpopulation and was at least partially due to increased apoptosis. Residual NK cells showed lower expression of activating Ly49 receptors and normal (liver) or decreased (spleen) IFN-c production. Nevertheless, NK cells from CD70-Tg mice displayed higher YAC-1 killing capacities. CD70-Tg NK cells exhibited up-regulated expression of NKG2D, which is in accordance with the increased YAC-1 lysis, as this is mainly NKG2D-dependent. Taken together, this study is the first to demonstrate that continuous CD70 triggering of CD27 on NK cells in vivo results in a severe reduction of NK cells. On a single cell basis, however, residual NK cells display enhanced cytotoxicity.Key words: CD70-Tg mice . Cytotoxicity . Differentiation Supporting Information available online Introduction NK cells are large granular lymphocytes of the innate immune system that play a crucial role in the early host defense [1,2]. Upon activation, they directly eliminate target cells through exocytosis of perforin-and granzyme-containing granules, or by Fas ligand (CD178) or TRAIL pathways [3][4][5][6][7]. NK cells also produce cytokines and chemokines, which enable them to recruit non-specific haematopoetic cells, activate dendritic cells and prime adaptive lymphocytes [8][9][10][11]. As such, NK cells bridge between innate and adaptive immunity. The functional behaviour of NK cells is regulated by the engagement of a broad array of activating and inhibitory cell membrane receptors (reviewed in Lanier [12]).The BM is considered to be the main site for NK cell development [13][14][15][16]. Here, multipotent haematopoietic precursors generate NK cell precursors (NKP). Murine NKP are lineage(lin) À CD122 1 NK1.1 À CD49b À . NKP differentiate into immature NK (iNK) cells, which exhibit a lin À CD122 1 NK1. [20,21]. Interestingly, Hayakawa and Smyth [22]showed that within the TCR b À NK1.1 1 gated NK cell pool there is a CD11b low subpopulation, including both iNK and early mNK cells, which is homogenously CD27 high (referred to as subset 1), whereas the CD11b high population of late mNK cells consists of two functionally distinct subsets: i.e. CD27 high (referred to as subset 2) and CD27 low (referred to as subset 3). NK cells from subset 1 are the first NK cell population detected after BM transplantation and they give rise to subset 2 after adoptive transfer. Subset 2 consists of fu...

show abstract

“…Despite the data collected on their function, relatively little is known about how the expression of these genes is regulated. Previous studies have shown that nearly all fetal mouse NK cells express CD94/NKG2 on their surface (18) before there is any detectable expression of the Ly-49 genes, with the exception of Ly-49e (19,20). This high frequency of expression decreases after birth, when Ly-49 expression begins to approach adult levels (21,22), and so it appears that there is a developmental switch between the predominate receptors expressed by mouse NK cells.…”

mentioning

confidence: 96%

Transcriptional Control of MurineCD94Gene: Differential Usage of Dual Promoters by Lymphoid Cell Types

Wilhelm

Landry

Takei

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

The CD94 gene product is involved in controlling NK cell activation, and is one of a family of immune receptors that is found in the NK gene complex in both humans and mice, adjacent to members of the NKG2 family. CD94 forms a heterodimeric complex with several members of the NKG2 family on the surface of NK, T, and NKT cells. These complexes recognize the nonclassical MHC class I molecules HLA-E and Qa-1b in humans and mice, respectively. The mechanism for cell type-specific expression of CD94 and other genes from the NK gene complex has not yet been elucidated. In the current study, we show that the murine CD94 gene has two promoters, one of which is upstream of a previously unidentified exon. We illustrate by quantitative real-time PCR that lymphoid cell types use these two promoters differentially and that the promoter usage seen in adult cells is already established during fetal development. We determined that the differential promoter usage by NK cells appears to be susceptible to perturbation, as both the murine NK cell line LNK, as well as cultured C57BL/6 NK cells showed altered promoter usage relative to fresh NK cells. Furthermore, the promoter activity observed in transfection assays did not correlate with expression of the endogenous CD94 gene, suggesting the involvement of chromatin structure/methylation in transcriptional regulation. Our detection of DNase I hypersensitive sites at the CD94 locus that are present only in a cell line expressing endogenous CD94 supports this hypothesis.

show abstract

Expression of Ly49E and CD94/NKG2 on Fetal and Adult NK Cells

Cited by 59 publications

References 69 publications

Interactions of Ly49 Family Receptors with MHC Class I Ligands in trans and cis

Interactions of Ly49 Family Receptors with MHC Class I Ligands in trans and cis

Continuous CD27 triggering in vivo strongly reduces NK cell numbers

Transcriptional Control of MurineCD94Gene: Differential Usage of Dual Promoters by Lymphoid Cell Types

Contact Info

Product

Resources

About