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  1. Buch ; Online ; Dissertation / Habilitation: Natural Killer Cell-Mediated Target Cell Killing in the Context of Viral Infections

    Hagemann, Kerri [Verfasser] / Altfeld, Marcus [Akademischer Betreuer]

    2022  

    Verfasserangabe Kerri Hagemann ; Betreuer: Marcus Altfeld
    Schlagwörter Biowissenschaften, Biologie ; Life Science, Biology
    Thema/Rubrik (Code) sg570
    Sprache Englisch
    Verlag Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky
    Erscheinungsort Hamburg
    Dokumenttyp Buch ; Online ; Dissertation / Habilitation
    Datenquelle Digitale Dissertationen im Internet

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  2. Artikel ; Online: HIV-1 Nef-mediated downregulation of CD155 results in viral restriction by KIR2DL5+ NK cells.

    Fittje, Pia / Hœlzemer, Angelique / Garcia-Beltran, Wilfredo F / Vollmers, Sarah / Niehrs, Annika / Hagemann, Kerri / Martrus, Glòria / Körner, Christian / Kirchhoff, Frank / Sauter, Daniel / Altfeld, Marcus

    PLoS pathogens

    2022  Band 18, Heft 6, Seite(n) e1010572

    Abstract: Antiviral NK cell activity is regulated through the interaction of activating and inhibitory NK cell receptors with their ligands on infected cells. HLA class I molecules serve as ligands for most killer cell immunoglobulin-like receptors (KIRs), but no ... ...

    Abstract Antiviral NK cell activity is regulated through the interaction of activating and inhibitory NK cell receptors with their ligands on infected cells. HLA class I molecules serve as ligands for most killer cell immunoglobulin-like receptors (KIRs), but no HLA class I ligands for the inhibitory NK cell receptor KIR2DL5 have been identified to date. Using a NK cell receptor/ligand screening approach, we observed no strong binding of KIR2DL5 to HLA class I or class II molecules, but confirmed that KIR2DL5 binds to the poliovirus receptor (PVR, CD155). Functional studies using primary human NK cells revealed a significantly decreased degranulation of KIR2DL5+ NK cells in response to CD155-expressing target cells. We subsequently investigated the role of KIR2DL5/CD155 interactions in HIV-1 infection, and showed that multiple HIV-1 strains significantly decreased CD155 expression levels on HIV-1-infected primary human CD4+ T cells via a Nef-dependent mechanism. Co-culture of NK cells with HIV-1-infected CD4+ T cells revealed enhanced anti-viral activity of KIR2DL5+ NK cells against wild-type versus Nef-deficient viruses, indicating that HIV-1-mediated downregulation of CD155 renders infected cells more susceptible to recognition by KIR2DL5+ NK cells. These data show that CD155 suppresses the antiviral activity of KIR2DL5+ NK cells and is downmodulated by HIV-1 Nef protein as potential trade-off counteracting activating NK cell ligands, demonstrating the ability of NK cells to counteract immune escape mechanisms employed by HIV-1.
    Mesh-Begriff(e) Antiviral Agents/metabolism ; Down-Regulation ; HIV Infections ; HIV Seropositivity ; HIV-1 ; Humans ; Killer Cells, Natural ; Ligands ; Receptors, Natural Killer Cell/metabolism ; Receptors, Virus ; nef Gene Products, Human Immunodeficiency Virus/genetics ; nef Gene Products, Human Immunodeficiency Virus/metabolism
    Chemische Substanzen Antiviral Agents ; Ligands ; Receptors, Natural Killer Cell ; Receptors, Virus ; nef Gene Products, Human Immunodeficiency Virus ; nef protein, Human immunodeficiency virus 1 ; nef protein, Human immunodeficiency virus 2 ; poliovirus receptor
    Sprache Englisch
    Erscheinungsdatum 2022-06-24
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1010572
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: The co-inhibitory receptor TIGIT regulates NK cell function and is upregulated in human intrahepatic CD56

    Ziegler, Annerose E / Fittje, Pia / Müller, Luisa M / Ahrenstorf, Annika E / Hagemann, Kerri / Hagen, Sven H / Hess, Leonard U / Niehrs, Annika / Poch, Tobias / Ravichandran, Gevitha / Löbl, Sebastian M / Padoan, Benedetta / Brias, Sébastien / Hennesen, Jana / Richard, Myrtille / Richert, Laura / Peine, Sven / Oldhafer, Karl J / Fischer, Lutz /
    Schramm, Christoph / Martrus, Glòria / Bunders, Madeleine J / Altfeld, Marcus / Lunemann, Sebastian

    Frontiers in immunology

    2023  Band 14, Seite(n) 1117320

    Abstract: The crosstalk between NK cells and their surrounding environment is enabled through activating and inhibitory receptors, which tightly control NK cell activity. The co-inhibitory receptor TIGIT decreases NK cell cytotoxicity and is involved in NK cell ... ...

    Abstract The crosstalk between NK cells and their surrounding environment is enabled through activating and inhibitory receptors, which tightly control NK cell activity. The co-inhibitory receptor TIGIT decreases NK cell cytotoxicity and is involved in NK cell exhaustion, but has also been associated with liver regeneration, highlighting that the contribution of human intrahepatic CD56
    Mesh-Begriff(e) Humans ; CD56 Antigen/metabolism ; Killer Cells, Natural/metabolism ; Liver/metabolism ; Receptors, Immunologic/genetics ; Receptors, Immunologic/metabolism ; Flow Cytometry
    Chemische Substanzen CD56 Antigen ; Receptors, Immunologic ; TIGIT protein, human
    Sprache Englisch
    Erscheinungsdatum 2023-02-09
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1117320
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Natural killer cell-mediated ADCC in SARS-CoV-2-infected individuals and vaccine recipients.

    Hagemann, Kerri / Riecken, Kristoffer / Jung, Johannes M / Hildebrandt, Heike / Menzel, Stephan / Bunders, Madeleine J / Fehse, Boris / Koch-Nolte, Friedrich / Heinrich, Fabian / Peine, Sven / Schulze Zur Wiesch, Julian / Brehm, Thomas T / Addo, Marylyn M / Lütgehetmann, Marc / Altfeld, Marcus

    European journal of immunology

    2022  Band 52, Heft 8, Seite(n) 1297–1307

    Abstract: COVID-19, caused by SARS-CoV-2, has emerged as a global pandemic. While immune responses of the adaptive immune system have been in the focus of research, the role of NK cells in COVID-19 remains less well understood. Here, we characterized NK cell- ... ...

    Abstract COVID-19, caused by SARS-CoV-2, has emerged as a global pandemic. While immune responses of the adaptive immune system have been in the focus of research, the role of NK cells in COVID-19 remains less well understood. Here, we characterized NK cell-mediated SARS-CoV-2 antibody-dependent cellular cytotoxicity (ADCC) against SARS-CoV-2 spike-1 (S1) and nucleocapsid (NC) protein. Serum samples from SARS-CoV-2 resolvers induced significant CD107a-expression by NK cells in response to S1 and NC, while serum samples from SARS-CoV-2-negative individuals did not. Furthermore, serum samples from individuals that received the BNT162b2 vaccine induced strong CD107a expression by NK cells that increased with the second vaccination and was significantly higher than observed in infected individuals. As expected, vaccine-induced responses were only directed against S1 and not against NC protein. S1-specific CD107a responses by NK cells were significantly correlated to NK cell-mediated killing of S1-expressing cells. Interestingly, screening of serum samples collected prior to the COVID-19 pandemic identified two individuals with cross-reactive antibodies against SARS-CoV-2 S1, which also induced degranulation of NK cells. Taken together, these data demonstrate that antibodies induced by SARS-CoV-2 infection and anti-SARS-CoV-2 vaccines can trigger significant NK cell-mediated ADCC activity, and identify some cross-reactive ADCC-activity against SARS-CoV-2 by endemic coronavirus-specific antibodies.
    Mesh-Begriff(e) Antibodies, Viral/metabolism ; Antibody-Dependent Cell Cytotoxicity ; BNT162 Vaccine ; COVID-19 ; Humans ; Killer Cells, Natural ; Pandemics ; SARS-CoV-2
    Chemische Substanzen Antibodies, Viral ; BNT162 Vaccine (N38TVC63NU)
    Sprache Englisch
    Erscheinungsdatum 2022-04-22
    Erscheinungsland Germany
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.202149470
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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