elisabgb

• Henden, Camilla; Fjerdingstad, Hege Brincker; Bjørnsen, Elisabeth Gyllensten; Thiruchelvam-Kyle, Lavanya; Daws, Michael Rory & Inngjerdingen, Marit [Vis alle 8 forfattere av denne artikkelen] (2025). NK-cell cytotoxicity toward pluripotent stem cells and their neural progeny: impacts of activating and inhibitory receptors and KIR/HLA mismatch. Stem Cells. ISSN 1066-5099. 43(3). doi: 10.1093/stmcls/sxae083. Fulltekst i vitenarkiv Vis sammendrag

  Pluripotent stem cells provide opportunities for treating injuries and previously incurable diseases. A major concern is the immunogenicity of stem cells and their progeny. Here, we have dissected the molecular mechanisms that allow natural killer (NK) cells to respond to human pluripotent stem cells, investigating a wide selection of activating and inhibitory NK-cell receptors and their ligands. Reporter cells expressing the activating receptor NKG2D responded strongly to embryonic stem (ES) cell lines and induced pluripotent stem (iPS) cell lines, whereas reporter cells expressing the activating receptors NKp30, NKp46, KIR2DS1, KIR2DS2, and KIR2DS4 did not respond. Human ES and iPS cells invariably expressed several ligands for NKG2D. Expression of HLA-C and HLA-E was lacking or low, insufficient to trigger reporter cells expressing the inhibitory receptors KIR2DL1, -2DL2, or -2DL3. Similar results were obtained for the pluripotent embryonic carcinoma cell lines NTERA-2 and 2102Ep, and also iPS-cell-derived neural progenitor cells. Importantly, neural progenitor cells and iPS-cell-derived motoneurons also expressed B7H6, the ligand for the activating receptor NKp30. In line with these observations, IL-2-stimulated NK cells showed robust cytotoxic responses to ES and iPS cells as well as to iPS-cell-derived motoneurons. No significant differences in cytotoxicity levels were observed between KIR/HLA matched and mismatched combinations of NK cells and pluripotent targets. Together, these data indicate that pluripotent stem cells and their neural progeny are targets for NK-cell killing both by failing to sufficiently express ligands for inhibitory receptors and by expression of ligands for activating receptors.

• Bjørnsen, Elisabeth Gyllensten; Thiruchelvam-Kyle, Lavanya; Hoelsbrekken, Sigurd Erik; Henden, Camilla; Sæther, Per Christian & Boysen, Preben [Vis alle 8 forfattere av denne artikkelen] (2019). B7H6 is a functional ligand for NKp30 in rat and cattle and determines NKp30 reactivity toward human cancer cell lines. European Journal of Immunology. ISSN 0014-2980. 49(1), s. 54–65. doi: 10.1002/eji.201847746. Fulltekst i vitenarkiv Vis sammendrag

  NK cells kill cancer cells and infected cells upon activation by cell surface receptors. Human NKp30 is an activating receptor expressed by all mature NK cells. The B7 family member B7H6 has been identified as one ligand for NKp30. Several alternative ligands have also been reported, and the field remains unsettled. To this end, we have identified full‐length functional B7H6 orthologs in rat and cattle, demonstrated by phylogenetic analysis and transfection experiments. In cell–cell contact‐dependent assays, chimeric NKp30 reporter cells responded strongly to B7H6 in rat and cattle. Likewise, rat NKp30 expressing target cells induced strong activation of B7H6 reporter cells. Together, these observations demonstrate that B7H6 is conserved as a functional ligand for NKp30 in mammalian species separated by more than 100 million years of evolution. B7H6 and NKp30 are pseudogenes in laboratory mice. The rat thus represents an attractive experimental animal model to study the NKp30‐B7H6 interaction in vivo. B7H6 was widely expressed among human cancer cell lines, and the expression level correlated strongly with the activation of human NKp30 reporter cells. Furthermore, siRNA knockdown of B7H6 abolished NKp30 reporter responses, suggesting that B7H6 is the major functionally relevant expressed ligand for NKp30 on these cancer cell lines.

• Knutsen, Linn Emilie; Dissen, Erik; Sæther, Per Christian; Bjørnsen, Elisabeth Gyllensten; Pialek, Jaroslav & Storset, Anne [Vis alle 7 forfattere av denne artikkelen] (2018). Evidence of functional Cd94 polymorphism in a free-living house mouse population. Immunogenetics. ISSN 0093-7711. s. 1–13. doi: 10.1007/s00251-018-01100-x. Fulltekst i vitenarkiv Vis sammendrag

  The CD94 receptor, expressed on natural killer (NK) and CD8+ T cells, is known as a relatively non-polymorphic receptor with orthologues in humans, other primates, cattle, and rodents. In the house mouse (Mus musculus), a single allele is highly conserved among laboratory strains, and reports of allelic variation in lab- or wild-living mice are lacking, except for deficiency in one lab strain (DBA/2J). The non-classical MHC-I molecule Qa-1b is the ligand for mouse CD94/NKG2A, presenting alternative non-americ fragment of leader peptides (Qa-1 determinant modifier (Qdm)) from classical MHC-I molecules. Here, we report a novel allele identified in free-living house mice captured in Norway, living among individuals carrying the canonical Cd94 allele. The novel Cd94LocA allele encodes 12 amino acid substitutions in the extracellular lectin-like domain. Flow cytometric analysis of primary NK cells and transfected cells indicates that the substitutions prevent binding of CD94 mAb and Qa-1b/Qdm tetramers. Our data further indicate correlation of Cd94 polymorphism with the two major subspecies of house mice in Europe. Together, these findings suggest that the Cd94LocA/NKG2A heterodimeric receptor is widely expressed among M. musculus subspecies musculus, with ligand-binding properties different from mice of subspecies domesticus, such as the C57BL/6 strain.

• Thiruchelvam-Kyle, Lavanya; Hoelsbrekken, Sigurd Erik; Sæther, Per Christian; Bjørnsen, Elisabeth Gyllensten; Pende, Daniela & Fossum, Sigbjørn [Vis alle 8 forfattere av denne artikkelen] (2017). The Activating Human NK Cell Receptor KIR2DS2 Recognizes a β2-Microglobulin–Independent Ligand on Cancer Cells. Journal of Immunology. ISSN 0022-1767. 198(7), s. 2556–2567. doi: 10.4049/jimmunol.1600930. Fulltekst i vitenarkiv

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