Genomic analysis of MIC genes in rhesus macaques

Seo, J.-W.; Walter, Lutz; Günther, Eberhard

doi:10.1034/j.1399-0039.2001.580303.x

Cited by 16 publications

(20 citation statements)

References 21 publications

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“…Also, preliminary analysis of a porcine bacteria artificial chromosome clone suggests several additional loci encoding ULBP-like proteins (our unpublished observations). In this regard, pigs appear similar to humans, in which several ULBP and MIC proteins serve as ligands for NKG2D (26,27), and also mice, cattle, and primates, which express several NKG2D ligands (46,47). The redundancy of the NKG2D system within a species might be driven by immune evasion mechanisms of pathogens such as CMV.…”

Section: Discussionmentioning

confidence: 99%

Porcine UL16-Binding Protein 1 Expressed on the Surface of Endothelial Cells Triggers Human NK Cytotoxicity through NKG2D

Lilienfeld

Garcia-Borges

Crew

2006

The Journal of Immunology

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Cellular rejection mechanisms, including NK cells, remain a hurdle for successful pig-to-human xenotransplantation. Human anti-pig NK cytotoxicity depends on the activating receptor NKG2D. Porcine UL16-binding protein 1 (pULBP1) and porcine MHC class I chain-related protein 2 (pMIC2) are homologues of the human NKG2D ligands ULBP 1–4 and MICA and B, respectively. Although transcribed in porcine endothelial cells (pEC), it is not known whether pULBP1 and pMIC2 act as functional ligands for human NKG2D. In this study, surface protein expression of pULBP1 was demonstrated by flow cytometry using a novel pULBP1-specific polyclonal Ab and by cellular ELISA using NKG2D-Fc fusion protein. Reciprocally, pULBP1-Fc bound to primary human NK cells, whereas pMIC2-Fc did not. Transient and stable down-regulation of pULBP1 mRNA in pEC using short-interfering RNA oligonucleotide duplexes and short hairpin RNA, respectively, resulted in a partial inhibition of xenogeneic NK cytotoxicity through NKG2D in 51Cr release assays. In contrast, down-regulation of pMIC2 mRNA did not inhibit NK cytotoxicity. Human NK cytotoxicity against pEC mediated by freshly isolated or IL-2-activated NK cells through NKG2D was completely blocked using anti-pULBP1 polyclonal Ab. In conclusion, this study suggests that pULBP1 is the predominant, if not only, functional porcine ligand for human NKG2D. Thus, the elimination of pULBP1 on porcine tissues represents an attractive target to protect porcine xenografts from human NK cytotoxicity.

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Section: Discussionmentioning

confidence: 99%

Porcine UL16-Binding Protein 1 Expressed on the Surface of Endothelial Cells Triggers Human NK Cytotoxicity through NKG2D

Lilienfeld

Garcia-Borges

Crew

2006

The Journal of Immunology

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“…To induce MICA/B expression, the melanoma cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) with 10 μM of the histone deacetylase inhibitor suberoylanilide hydroxyamic acid (SAHA) (Qbiogene-Alexis, Grünberg, Germany) 20 hrs before being used for experiments [14]. Mouse L cells were co-transfected by electroporation with 30 μg of the cosmid A158 [15] containing the MICA gene of the rhesus macaque ( Macaca mulatta ) [16], and with 1 μg of the DsRed vector (Clontech, Heidelberg, Germany), which confers resistance to geneticin (G418, Invitrogen, Karlsruhe, Germany). After selection with geneticin (1 mg/ml), MICA expression was analysed in stable clones by flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

The endogenous danger signals HSP70 and MICA cooperate in the activation of cytotoxic effector functions of NK cells

Elsner

Flügge

Lozano

et al. 2010

J Cellular Molecular Medi

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Although natural killer (NK) cells are often described as first line defence against infected or malignant cells which act without the need of prior activation, it is known now that the NK cell activity is tightly regulated by other cells and soluble factors. We show here that the stress-inducible heat shock protein (HSP) 70 activates human NK cells to kill target cells expressing major histocompatibility complex class I chain-related molecule A (MICA) in a natural killer group 2 member D (NKG2D-) dependent manner. The HSP70-derived peptide TKD (TKDNNLLGRFELSG) was able to replace the full-length HSP70 and to exert the same function. Interestingly, the expression of the cytotoxic effector protease granzyme B in NK cells was increased after TKD stimulation. When MICA and MICB expression was induced in human tumour cells by a histone deacetylase inhibitor and NK cells were activated by HSP70 or TKD, both treatments jointly improved the killing of the tumour cells. Thus, the synergistic activity of two stress-inducible immunological danger signals, HSP70 and MICA/B, leads to activation and enhanced cytotoxicity of human NK cells against tumour cells.

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“…MICA and MICB are stress-inducible proteins whose expression is upregulated in certain tumors and infected cells (Groh et al, 1996(Groh et al, , 1999(Groh et al, , 2001. Mice apparently lack orthologs of MICA and MICB but the presence of MICA-and MICB-like genes are clearly apparent in primates (Steinle et al, 1998;Seo et al, 2001) and cattle (based on est sequences in GenBank). In Sus scrofa (the pig), two MICA/B-like genes have been identified (dubbed MIC1 and MIC2) from genomic sequencing efforts (Chardon et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Molecular cloning and characterization of a porcine UL16 binding protein (ULBP)-like cDNA

Garcia-Borges

Phanavanh

Saraswati

et al. 2005

Molecular Immunology

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UL16 binding proteins (ULBPs) are ligands for the NK cell activating receptor NKG2D. A cDNA encoding a porcine ULBP-like protein (PULBP) was cloned and the predicted amino acid sequence exhibited 35-52% identity to human ULBPs. Southern blot analysis suggested that there is only one ULBP-like gene in the pig genome. Transcripts of PULBP and another potential NKG2D ligand, MIC2, were detected by RT-PCR in a wide range of tissues. Recombinant PULBP-Fc and human ULBP2-Fc fusion proteins were made and used to examine PULBP binding to porcine PBMCs and a human NK cell line (NKL cells). PULBP-Fc bound to a subpopulation of porcine PBMCs but not NKL cells. Conversely, human ULBP2-Fc did not bind to porcine PBMCs but did stably interact with NKL cells.

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Genomic analysis of MIC genes in rhesus macaques

Cited by 16 publications

References 21 publications

Porcine UL16-Binding Protein 1 Expressed on the Surface of Endothelial Cells Triggers Human NK Cytotoxicity through NKG2D

Porcine UL16-Binding Protein 1 Expressed on the Surface of Endothelial Cells Triggers Human NK Cytotoxicity through NKG2D

The endogenous danger signals HSP70 and MICA cooperate in the activation of cytotoxic effector functions of NK cells

Molecular cloning and characterization of a porcine UL16 binding protein (ULBP)-like cDNA

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