Selective intracellular retention of virally induced NKG2D ligands by the human cytomegalovirus UL16 glycoprotein

Welte, S.; Sinzger, Christian; Lutz, Stefan; Singh‐Jasuja, Harpreet; Sampaio, Kerstin Laib; Eknigk, Ute; Rammensee, Hans‐Georg; Steinle, Alexander

doi:10.1002/immu.200390022

Cited by 216 publications

(206 citation statements)

References 31 publications

(62 reference statements)

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“…macrophages) or inducible by proinflammatory cytokines, and it is impaired by some virus molecules [53]. On the other hand, NKG2D ligands are displayed in HCMV-infected cells, and immune evasion mechanisms that interfere with their expression indirectly reflect the importance of the KLR in the anti-viral response [18,22,[27][28][29].…”

Section: Distribution Of Ilt2 Kir and Cd94/nkg2 Nkr On Hcmv-stimulatmentioning

confidence: 99%

“…The KLR activates NK cells and costimulates the response of CD8 + CTL against human cytomegalovirus (HCMV)-infected targets [18,26]; the identification of immune evasion mechanisms that interfere with surface expression of NKG2D ligands underline its importance in the antiviral response. The UL16 glycoprotein inhibits surface expression of MICB, ULBP1, ULBP2 [22,[27][28][29] and also interacts with RAET1G [24]. The gpUL142 HCMV molecule has been recently reported to down-regulate MICA [30].…”

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: Distribution Of Ilt2 Kir and Cd94/nkg2 Nkr On Hcmv-stimulatmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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“…2. Truncated NKG2D ligands such as this may have a role in blocking receptor interactions, and their expression could be part of an immune evasion strategy used by tumors or infected cells (2,6,25).…”

Section: Alternative Splicing Of Raet1gmentioning

confidence: 99%

“…The expression of UL16 is proposed as a mechanism by which HCMV may evade immune recognition by interfering with NKG2D binding to its ligands (9,25). Not all human MIC and ULBP proteins are targeted.…”

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confidence: 99%

Two Human ULBP/RAET1 Molecules with Transmembrane Regions Are Ligands for NKG2D

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et al. 2004

The Journal of Immunology

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We characterized two novel members of the RAET1/ULBP gene cluster, RAET1E and RAET1G. The encoded proteins were similar to the ULBP in their class I-like α1 and α2 domains, but differed in that, instead of being GPI-anchored, their sequences were type 1 membrane-spanning molecules. Both proteins were capable of being expressed at the cell surface. Both proteins bound the activating receptor NKG2D, and RAET1G bound the human CMV protein UL16. The expression of diverse NKG2D-binding molecules in different tissues and with different properties is consistent with multiple modes of infection- or stress-induced activation.

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“…28,[30][31][32][33] MICA expression also occurs in certain carcinomas, and has been found in hepatocellular cancer tissue and hepatoma cell lines. 34 In addition, in one study, MICA induction on dendritic cells was strongly impaired in persons with persistent HCV infection, compared with healthy controls.…”

Section: Introductionmentioning

confidence: 99%

MICA and recovery from hepatitis C virus and hepatitis B virus infections

et al. 2004

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The polymorphic MHC class I chain-related A (MICA) gene encodes a ligand that has different binding affinities for the NKG2D activating receptor of CD8 þ T cells and natural killer (NK) cells. We hypothesized that MICA heterogeneity would affect recovery from hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. To test the hypothesis, we initially typed known MICA polymorphisms for 228 persons who cleared HCV infection and 442 persons with persistent hepatitis C matched on other factors affecting viral persistence. Although MICA*015 was detected more than two-fold more often in persons with viral clearance (odds ratio 0.36, 95% confidence interval ¼ 0.19, 0.80), it occurred in fewer than 5% of the study population. In a similar analysis of 442 persons with chronic hepatitis B and 768 matched controls who recovered, MICA*015 was detected in 2.0% of persons with chronic hepatitis B and only 0.9% of controls. No significant associations were detected with other MICA polymorphisms. While further investigation may reveal a structural basis of the MICA*015 associations, these data provide little support for the hypothesis that differential distribution of MICA alleles substantially affects recovery from HCV and HBV infections.

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Selective intracellular retention of virally induced NKG2D ligands by the human cytomegalovirus UL16 glycoprotein

Cited by 216 publications

References 31 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

Two Human ULBP/RAET1 Molecules with Transmembrane Regions Are Ligands for NKG2D

MICA and recovery from hepatitis C virus and hepatitis B virus infections

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Selective intracellular retention of virally induced NKG2D ligands by the human cytomegalovirus UL16 glycoprotein

Cited by 216 publications

References 31 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

Two Human ULBP/RAET1 Molecules with Transmembrane Regions Are Ligands for NKG2D

MICA and recovery from hepatitis C virus and hepatitis B virus infections

Contact Info

Product

Resources

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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