ULBPs, Novel MHC Class I–Related Molecules, Bind to CMV Glycoprotein UL16 and Stimulate NK Cytotoxicity through the NKG2D Receptor

Cosman, David; Mullberg, Jürgen; Sutherland, Claire L.; Chin, Wilson; Armitage, Richard J.; Fanslow, William C.; Kubin, Marek; Chalupny, N. Jan

doi:10.1016/s1074-7613(01)00095-4

Cited by 1,099 publications

(461 citation statements)

References 39 publications

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“…UL40 is a late CMV protein which contains a signal peptide similar in its sequence to the signal peptide of HLA class I molecules and can restore cell surface HLA-E expression [7]. Moreover, two CMV proteins, UL142 [8] and UL16 [9], respectively, retain the MHC class I-related chain A (MICA) and chain B (MICB) proteins in the cytoplasm of CMV-infected cells, thus limiting NKG2D + NK cell attack. In addition, US18 and US20 target MICA for lysosomal degradation [10].…”

Section: Introductionmentioning

confidence: 99%

Cytomegalovirus-Infected Primary Endothelial Cells Trigger NKG2C<sup>+</sup> Natural Killer Cells

et al. 2016

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Among innate cells, natural killer (NK) cells play a crucial role in the defense against cytomegalovirus (CMV). In some individuals, CMV infection induces the expansion of NKG2C⁺ NK cells that persist after control of the infection. We have previously shown that KIR2DL⁺ NK cells, in contrast to NKG2C⁺ NK cells, contribute to controlling CMV infection using a CMV-infected monocyte-derived dendritic cell (MDDC) model. However, the nature of CMV-infected cells contributing to the expansion of the NKG2C⁺ NK cell subset remains unclear. To gain more insight into this question, we investigated the contribution of NKG2C⁺ NK cell activation by CMV-infected primary human aortic endothelial cells (EC) isolated from kidney transplant donors, which constitutively express the human leukocyte antigen (HLA)-E molecule. Here, we show that, although classic HLA class I expression was drastically downregulated, nonclassic HLA-E expression was maintained in CMV-infected EC. By comparing HLA expression patterns in CMV-infected EC, fibroblasts and MDDC, we demonstrate a cell-dependent modulation of HLA-E expression by CMV infection. NKG2C⁺ NK cell degranulation was significantly triggered by CMV-infected EC regardless of the nature of the HLA-E allele product. EC, predominantly present in vessels, may constitute a privileged site for CMV infection that drives a ‘memory' NKG2C⁺ NK cell subset.

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Section: Introductionmentioning

confidence: 99%

Cytomegalovirus-Infected Primary Endothelial Cells Trigger NKG2C<sup>+</sup> Natural Killer Cells

et al. 2016

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“…Ligands for NKG2D comprised human class I‐like molecules MICA, MICB, and ULBP, which are stress‐induced molecules expressed by tumors of epithelial origin and activate NK cell cytotoxicity through their NKG2D receptor 29, 30. Although we carried out immunohistochemistry using frozen sections as a preliminary experiment, evaluation of the expression of MICA, MICB, and ULBP2 in tumor tissue was challenging.…”

Section: Resultsmentioning

confidence: 99%

“…Non‐classical MHC class I antigens, such as MICA, MICB, and ULBP, can engage a stimulatory receptor on NK cells comprising a heterodimeric complex of NKG2D/DAP10, a cell‐surface adaptor molecule involved in signal transduction 29, 41. The activation signal resulting from the engagement of NKG2D‐DAP10 overrides the inhibitory signal from MHC class I molecules leading to target cell lysis 30, 42.…”

Section: Discussionmentioning

confidence: 99%

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis

Hirata

Ishiyama

Tanaka

et al. 2018

Annals of Gastroent Surgery

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AimWe investigated the chemotherapy effect of resectable colorectal cancer with liver metastasis (CRLM) on the function of intrahepatic immune cells.MethodsWe classified patients into adjuvant chemotherapy (bevacizumab+CapeOX) after hepatectomy group (group A) and neoadjuvant chemotherapy followed by hepatectomy group (group B), and collected peripheral blood mononuclear cells (PBMC) and liver mononuclear cells (LMNC) to ascertain phenotypic and functional differences.ResultsThere were no significant differences in lymphocyte fractions of either PBMC or LMNC between groups, except for the significantly lower percentage of natural killer (NK) cells in LMNC in group B than in group A. Significantly higher percentage of natural‐killer group 2, member D (NKG2D)‐ positive NK cells in PBMC and percentage of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐, NKp30‐, and signal regulatory protein β (SIRPβ)‐positive NK cells in LMNC were found in group B. Furthermore, significantly higher expressions of NKG2D and SIRPβ in peripheral blood NK cells and of NKp46 and CD122 in liver NK cells were found in group B. When LMNC were incubated with interleukin (IL)‐2 in vitro, no difference was observed in the expression of these molecules in NK cells between groups. Consistently, there was no difference in the cytotoxic activity of those LMNC against a colon adenocarcinoma cell line between groups.ConclusionColorectal cancer with liver metastasis patients treated with neoadjuvant chemotherapy showed enhanced expression of activation markers on peripheral blood and liver NK cells in comparison with patients who did not receive therapy; however, the difference in those function remains unclear. These results suggest that neoadjuvant chemotherapy does not have a negative impact on intrahepatic immune cells in resectable CRLM patients.

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“…In humans, there are two families of NKG2DL, the UL16-binding proteins (ULBP) [67] and the MHC class Ichain-related proteins A and B (MICA/B) [50;62;68]( Table 1). MIC genes (MICA to MICF) are located within the human MHC [69] (Fig.…”

Section: Nkg2d Ligands Of Mouse and Manmentioning

confidence: 99%

Danger-Detector NKG2D: Immunosurveillance of Induced Self and Modulation by Cytokines and Soluble Ligands

Steinle¹

2005

CMCAIAA

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The novel "induced self" recognition mode mediated by the immunoreceptor NKG2D allows NK cells to eliminate dangerous and dysfunctional cells. Long-puzzling, complex NK cell reactivity patterns can now be explainedat least in part -by the combined action of the molecular players of the "missing self" and "induced self" hypotheses. Accordingly, MHC class I down-regulation in concert with an upregulated expression of self-ligands of activating NK receptors renders cells susceptible for NK cytotoxicity. The C-type lectin-like, activating NK receptor NKG2D detects a variety of inducibly expressed MHC class I-related molecules on stressed, infected, or malignant cells, and subsequently triggers effector functions of NK cells. Recent experiments also underline an important function of NKG2D on CD8 αβ T cells in tumor immunosurveillance and in the pathogenesis of autoimmune diseases. Here, we review the current knowledge on NKG2D and its ligands (NKG2DL) with regard to their structure, expression, and function, refer to recent data on the involvement of NKG2D in anti-viral immune defence, tumor surveillance, and autoimmune phenomena, and outline emerging evidence on the modulation of NKG2D by cytokines and soluble NKG2DL.

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ULBPs, Novel MHC Class I–Related Molecules, Bind to CMV Glycoprotein UL16 and Stimulate NK Cytotoxicity through the NKG2D Receptor

Cited by 1,099 publications

References 39 publications

Cytomegalovirus-Infected Primary Endothelial Cells Trigger NKG2C<sup>+</sup> Natural Killer Cells

Cytomegalovirus-Infected Primary Endothelial Cells Trigger NKG2C<sup>+</sup> Natural Killer Cells

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis

Danger-Detector NKG2D: Immunosurveillance of Induced Self and Modulation by Cytokines and Soluble Ligands

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