A novel family of Ig-like receptors for HLA class I molecules that modulate function of lymphoid and myeloid cells

Colonna, Marco; Nakajima, Hideo; Navarro, Francisco; López‐Botet, Miguel

doi:10.1002/jlb.66.3.375

Cited by 155 publications

(118 citation statements)

References 70 publications

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“…Inhibitory receptors of human NK cells including CD94:NKG2A, killer Iglike receptors, and some leukocyte Ig-like receptors are specific for different HLA class I determinants (31)(32)(33). The major activating receptors are NKG2D, 2B4, and the natural cytotoxicity receptors NKp30, NKp46, and NKp44 (34 -41).…”

Section: Nkp46 and Nkg2d Recognition Of Infected Dendritic Cells Is Nmentioning

confidence: 99%

NKp46 and NKG2D Recognition of Infected Dendritic Cells Is Necessary for NK Cell Activation in the Human Response to Influenza Infection

Draghi

Pashine

Sanjanwala

et al. 2007

The Journal of Immunology

181

169

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At an early phase of viral infection, contact and cooperation between dendritic cells (DCs) and NK cells activates innate immunity, and also influences recruitment, when needed, of adaptive immunity. Influenza, an adaptable fast-evolving virus, annually causes acute, widespread infections that challenge the innate and adaptive immunity of humanity. In this study, we dissect and define the molecular mechanisms by which influenza-infected, human DCs activate resting, autologous NK cells. Three events in NK cell activation showed different requirements for soluble mediators made by infected DCs and for signals arising from contact with infected DCs. IFN-α was mainly responsible for enhanced NK cytolysis and also important for CD69 up-regulation, whereas IL-12 was necessary for enhancing IFN-γ production. Increased CD69 expression and IFN-γ production, but not increased cytolysis, required recognition of influenza-infected DCs by two NK cell receptors: NKG2D and NKp46. Abs specific for these receptors or their known ligands (UL16-binding proteins 1–3 class I-like molecules for NKG2D and influenza hemagglutinin for NKp46) inhibited CD69 expression and IFN-γ production. Activation of NK cells by influenza-infected DCs and polyinosinic:polycytidylic acid (poly(I:C))-treated DCs was distinguished. Poly(I:C)-treated DCs did not express the UL16-binding protein 3 ligand for NKG2D, and in the absence of the influenza hemagglutinin there was no involvement of NKp46.

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Section: Nkp46 and Nkg2d Recognition Of Infected Dendritic Cells Is Nmentioning

confidence: 99%

NKp46 and NKG2D Recognition of Infected Dendritic Cells Is Necessary for NK Cell Activation in the Human Response to Influenza Infection

Draghi

Pashine

Sanjanwala

et al. 2007

The Journal of Immunology

181

169

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“…10 An important mediator of the induction of immune tolerance is immunoglobulin-like transcript (ILT) 3 (also known as LILRB4, CD85k, or LIR-5), which is expressed on monocytes and antigen-presenting cells (APCs) such as macrophages and dendritic cells (DCs). 11,12 ILT3 expression marks tolerogenic DCs and has been reported to be elevated in APCs of cancer patients 13,14 and decreased in autoimmune diseases. 15,16 ILT3 is believed to signal via its immunoreceptor tyrosine-based inhibitory motifs (ITIMs).…”

Section: Introductionmentioning

confidence: 99%

Immunoglobulin-like transcript 3 is expressed by myeloid-derived suppressor cells and correlates with survival in patients with non-small cell lung cancer

et al. 2015

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Myeloid-derived suppressor cells (MDSCs) play an important role in immune suppression and accumulate under pathologic conditions such as cancer and chronic inflammation. They comprise a heterogeneous population of immature myeloid cells that exert their immunosuppressive function via a variety of mechanisms. Immunoglobulin-like transcript 3 (ILT3) is a receptor containing immunoreceptor tyrosine-based inhibition motifs (ITIMs) that can be expressed on antigen-presenting cells and is an important regulator of dendritic cell tolerance. ILT3 exists in a membrane-bound and a soluble form and can interact with a yet unidentified ligand on T cells and thereby induce T-cell anergy, regulatory T cells, or T suppressor cells. In this study, we analyzed freshly isolated peripheral blood mononuclear cells (PBMCs) of 105 patients with non-small cell lung cancer and 20 healthy controls and demonstrated for the first time that ILT3 is expressed on MDSCs. We show that increased levels of circulating MDSCs correlate with reduced survival. On the basis of ILT3 cell surface expression, an ILT3 low and ILT3 high population of polymorphonuclear (PMN)-MDSCs could be distinguished. Interestingly, in line with the immunosuppressive function of ILT3 on dendritic cells, patients with an increased proportion of PMN-MDSCs and an increased fraction of the ILT3 high subset had a shorter median survival than patients with elevated PMN-MDSC and a smaller ILT3 high fraction. No correlation between the ILT3 high subset and other immune variables was found. ILT3 expressed on MDSCs might reflect a previously unknown mechanism by which this cell population induces immune suppression and could therefore be an attractive target for immune intervention.

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“…Indeed, cross-linking Siglec-7 with a specific antibody can result in inhibition of NK cell cytotoxicity or proliferation of myelocytic leukemia cells (5,7). Human NK cells express several kinds of inhibitory receptors such as killer inhibitory receptors, leukocyte Ig-like receptors, and CD94/NKG2 (8,9). Most of these molecules recognize HLA class I molecules expressed on the surface of normal cells, protecting the cells from NK cell-mediated cytolysis.…”

mentioning

confidence: 99%

A Small Region of the Natural Killer Cell Receptor, Siglec-7, Is Responsible for Its Preferred Binding to α2,8-Disialyl and Branched α2,6-Sialyl Residues

Yamaji

Teranishi

Alphey

et al. 2002

Journal of Biological Chemistry

174

143

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Siglec-7 is a sialic acid-binding lectin recently identified as an inhibitory receptor on natural killer cells.Here we characterize the sugar-binding specificity of Siglec-7 expressed on Chinese hamster ovary cells using polyvalent streptavidin-based glyco-probes. Glycoprobes carrying unique oligosaccharide structures such as GD3 (NeuAc␣2,8NeuAc␣2,3Gal␤1,4Glc) and LSTb (Gal␤1,3[NeuAc␣2,6]GlcNAc␤1,3Gal␤1,4Glc) oligosaccharides bound to Siglec-7 better than those carrying LSTc (NeuAc␣2,6Gal␤1,4GlcNAc␤1,3Gal␤1,4Glc) or GD1a (NeuAc␣2,3Gal␤1,3GalNAc␤1,4[NeuAc␣2,3]Gal-␤1,4Glc) oligosaccharides. In contrast, Siglec-9, which is 84% identical to Siglec-7, did not bind to the GD3 and LSTb probes but did bind to the LSTc and GD1a probes. To identify a region(s) responsible for their difference in binding specificity, we prepared a series of V-set domain chimeras between Siglecs-7 and -9. Substitution of a small region, Asn 70 -Lys 75 , of Siglec-7 with the equivalent region of Siglec-9 resulted in loss of Siglec-7-like binding specificity and acquisition of Siglec-9-like binding properties. In comparison, a Siglec-9-based chimera, which contains Asn 70 -Lys 75 with additional amino acids derived from Siglec-7, exhibited Siglec-7-like specificity. These results, combined with molecular modeling, suggest that the C-C loop in the sugar-binding domain plays a major role in determining the binding specificities of Siglecs-7 and -9.

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A novel family of Ig-like receptors for HLA class I molecules that modulate function of lymphoid and myeloid cells

Cited by 155 publications

References 70 publications

NKp46 and NKG2D Recognition of Infected Dendritic Cells Is Necessary for NK Cell Activation in the Human Response to Influenza Infection

NKp46 and NKG2D Recognition of Infected Dendritic Cells Is Necessary for NK Cell Activation in the Human Response to Influenza Infection

Immunoglobulin-like transcript 3 is expressed by myeloid-derived suppressor cells and correlates with survival in patients with non-small cell lung cancer

A Small Region of the Natural Killer Cell Receptor, Siglec-7, Is Responsible for Its Preferred Binding to α2,8-Disialyl and Branched α2,6-Sialyl Residues

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