Paired inhibitory and triggering NK cell receptors for HLA class I molecules

López‐Botet, Miguel; Bellón, Teresa; Llano, Manuel; Navarro, Francisco; Garcı́a, Pilar; Miguel, Marı́a de

doi:10.1016/s0198-8859(99)00161-5

Cited by 90 publications

(72 citation statements)

References 106 publications

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“…CD4 + T cells were incubated in 96-well plates (10 5 cells/well) in the presence of the indicated plate-bound antibodies (x-axis), as described in the Materials and methods. (A) Cultures were labelled with 3 HTdR at 48 h and harvested 18 h later. (B-C) IFN-c and TNF-a were analysed by ELISA in supernatants harvested at 48 h. Data correspond to samples from two donors containing 25% (donor #1) and 45% (donor #5) CD4 + NKG2D + cells that were independently analysed in different experiments; cells from a third individual that did not display NKG2D were tested as a control (NKG2D -).…”

Section: Discussionmentioning

confidence: 99%

“…In every case, supernatants were harvested after 48 h, and production of IFN-c and TNF-a was analysed by ELISA (Human IFNc Module Set and Human TNFa Module Set; Bender MedSystems, San Bruno CA). As described [13], 3 [H]-Thymidine ( 3 HTdR) was added (1 lCi/well) at 48 h, and cultures were further incubated for 18 h at 37 C; cells were harvested, and 3 HTdR incorporation was measured in a b-counter (LKB Wallac, Turku, Finland).…”

Section: Immunofluorescence and Flow Cytometry Analysismentioning

confidence: 99%

“…Some T lymphocyte subsets share with NK cells the expression of inhibitory and activating receptors specific for HLA class I molecules, such as killer immunoglobulin-like receptors (KIR), CD94/NKG2A, CD94/NKG2C and ILT2 (LIR1, CD85j) [1][2][3][4]. NK cell receptors (NKR) have been detected in TCRcd + cells as well as TCRab + CD8 + and CD4 + lymphocytes with an effector-memory phenotype [5][6][7][8], including virus-specific cytotoxic T lymphocytes (CTL) [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Expression and function of NKG2D in CD4⁺ T cells specific for human cytomegalovirus

et al. 2006

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The human NKG2D killer lectin‐like receptor (KLR) is coupled by the DAP10 adapter to phosphoinositide 3‐kinase (PI3 K) and specifically interacts with different stress‐inducible molecules (i.e. MICA, MICB, ULBP) displayed by some tumour and virus‐infected cells. This KLR is commonly expressed by human NK cells as well as TCRγδ+ and TCRαβ+CD8+ T lymphocytes, but it has been also detected in CD4+ T cells from rheumatoid arthritis and cancer patients. In the present study, we analysed NKG2D expression in human cytomegalovirus (HCMV)‐specific CD4+ T lymphocytes. In vitro stimulation of peripheral blood mononuclear cells (PBMC) from healthy seropositive individuals with HCMV promoted variable expansion of CD4+NKG2D+ T lymphocytes that coexpressed perforin. NKG2D was detected in CD28– and CD28dull subsets and was not systematically associated with the expression of other NK cell receptors (i.e. KIR, CD94/NKG2 and ILT2). Engagement of NKG2D with specific mAb synergized with TCR‐dependent activation of CD4+ T cells, triggering proliferation and cytokine production (i.e. IFN‐γ and TNF‐α). Altogether, the data support the notion that NKG2D functions as a prototypic costimulatory receptor in a subset of HCMV‐specific CD4+ T lymphocytes and thus may have a role in the response against infected HLA class II+ cells displaying NKG2D ligands.

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Section: Discussionmentioning

confidence: 99%

Section: Immunofluorescence and Flow Cytometry Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression and function of NKG2D in CD4⁺ T cells specific for human cytomegalovirus

et al. 2006

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“…All of the latter three are nonpolymorphic and are encoded telomeric of the HLA-A locus. HLA-C and HLA-E function to stimulate the inhibitory KIR and CD94/NKGA receptors found on NK cells, respectively (8). The function of HLA-F is unknown.…”

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confidence: 99%

HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells

Houser²,

Nicotra³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

177

150

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Human decidual CD14 ؉ macrophages and CD56 ؉ NK cells were isolated from material obtained after first-trimester pregnancy terminations. Each cell type expressed a specific surface receptor for histocompatibility leukocyte antigen (HLA)-G (an MHC class Ib protein that is expressed on extravillous trophoblasts), LILRB1 on CD14 ؉ macrophages and KIR2DL4 on CD56 ؉ NK cells. Cross-linking with anti-LILRB1 or anti-KIR2DL4 resulted in up-regulation of a small subset of mRNAs including those for IL-6, IL-8, and TNF␣ detected using a microarray representing 114 cytokines. Incubation with transfectants expressing the HLA-G homodimer (but not with transfectants expressing the HLA-G monomer) resulted in secretion of the same cytokine proteins from both leukocyte sets. Moreover, cytokine secretion from both leukocyte sets was blocked by both the appropriate anti-receptor mAb and by anti-HLA-G. The amount of these cytokines secreted by decidual macrophages was substantially greater than that secreted by decidual NK cells. VEGF was constitutively secreted by both cell types. LILRB1, which contains an immunoreceptor tyrosine-based switch motif, functions here as an activating receptor, although it has been known as an inhibitory receptor. KIR2DL4 also functions as an activating receptor, although it also has the potential to function as an inhibitory receptor. Secretion of proinflammatory and proangiogenic proteins supports a role for these leukocytes in important processes that are essential for successful pregnancy, but they may represent only a portion of the proteins that are secreted.IL-6 ͉ IL-8 ͉ pregnancy ͉ trophoblast ͉ VEGF

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“…The first group includes several multigenic families of receptors (killer Ig-related receptor, Ig-like transcript, receptor for IgA Fc and leukocyte-associated Ig-like receptor) that are encoded within the leukocyte receptor complex on chromosome 19 (19q13.4), as well as other gene families (i.e., signal-regulatory protein (SIRP), paired Ig-like receptor, and the family of triggering receptors expressed by myeloid cells (TREM) 4 ) located in different chromosomes (1,2,4). Lectin-like receptors comprise, among others, CD94/NKG2s heterodimers and members of the Ly49 family (5,6).…”

mentioning

confidence: 99%

Molecular Characterization of a Novel Immune Receptor Restricted to the Monocytic Lineage

Aguilar

Álvarez-Errico

García‐Montero

et al. 2004

The Journal of Immunology

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Homology basic local alignment search tool search was conducted using a sequence encoding for a novel inhibitory receptor (IREM-1) cloned in our laboratory and a previously described homologous sequence termed CMRF-35. On the basis of this information, we cloned a full length cDNA corresponding to a novel member of this family, termed immune receptor expressed by myeloid cells 2 (IREM-2). The gene, located in chromosome 17q25.1, encodes for a protein of 205 aa that contains an extracellular region comprising an Ig-like domain and a transmembrane region with a positively charged amino acid residue (lysine), that predicted its putative association with an adapter molecule. Indeed, the interaction between IREM-2 and DAP-12 was confirmed in transfected COS-7 cells. By generating specific Abs and using bone marrow and PBMCs, we observed that IREM-2 expression appeared to be restricted to mature hemopoietic cells of the monocytic and myeloid dendritic cell lineages. In vitro differentiation to macrophages or immature dendritic cells down-regulated IREM-2 expression. Upon engagement with the specific mAbs, IREM-2 expressed in rat basophilic leukemia cells together with DAP-12, induced NFAT transcriptional activity; moreover, IREM-2 engagement on monocytes induced TNF-α production. Taken together, our results indicate that IREM-2 is a novel activating receptor of the Ig-superfamily in the monocytic lineage.

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Paired inhibitory and triggering NK cell receptors for HLA class I molecules

Cited by 90 publications

References 106 publications

Expression and function of NKG2D in CD4⁺ T cells specific for human cytomegalovirus

Expression and function of NKG2D in CD4⁺ T cells specific for human cytomegalovirus

HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells

Molecular Characterization of a Novel Immune Receptor Restricted to the Monocytic Lineage

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Paired inhibitory and triggering NK cell receptors for HLA class I molecules

Cited by 90 publications

References 106 publications

Expression and function of NKG2D in CD4+ T cells specific for human cytomegalovirus

Expression and function of NKG2D in CD4+ T cells specific for human cytomegalovirus

HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells

Molecular Characterization of a Novel Immune Receptor Restricted to the Monocytic Lineage

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Expression and function of NKG2D in CD4⁺ T cells specific for human cytomegalovirus

Expression and function of NKG2D in CD4⁺ T cells specific for human cytomegalovirus