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Open Access Publications from the University of California

Scholarly Works (13 results)

  • Article
  • Peer Reviewed
UC San Francisco Previously Published Works (2005)

Irradiation-resistant natural killer (NK) cells in an F(1) recipient can reject parental bone marrow, and host NK cells can also prevent engraftment of allogeneic bone marrow. We show here that repopulating bone marrow cells in certain mouse strains expressed retinoic acid early inducible 1 proteins, which are ligands for the activating NKG2D NK cell receptor. Treatment with a neutralizing antibody to NKG2D prevented rejection of parental BALB/c bone marrow in (C57BL/6 x BALB/c) F(1) recipients and allowed engraftment of allogeneic BALB.B bone marrow in C57BL/6 recipients. Additionally, bone marrow from C57BL/6 mice transgenic for retinoic acid early inducible 1epsilon was rejected by syngeneic mice but was accepted after treatment with antibody to NKG2D. If other stem cells or tissues upregulate expression of NKG2D ligands after transplantation, NKG2D may contribute to graft rejection in immunocompetent hosts.

    Cover page: Function of NKG2D in natural killer cell-mediated rejection of mouse bone marrow grafts.
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2018)
      Cover page: Pillars Article: Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICA. Science. 1999. 285: 727-729.
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2000)
      Many of the activating receptors on natural killer (NK) cells are multisubunit complexes composed of ligand-binding receptors that are noncovalently associated with membrane-bound signaling adaptor proteins, including CD3zeta, FcstraightepsilonRIgamma, DAP12, and DAP10. Because the DAP10 and DAP12 genes are closely linked, expressed in NK cells, and have remarkably similar transmembrane segments, it was of interest to determine the specificity of their interactions with ligand-binding receptors and to examine their signaling properties. Despite their similarities, DAP10, DAP12, FcstraightepsilonRIgamma, and CD3zeta form specific receptor complexes with their ligand-binding partners in NK cells and transfectants. The transmembrane regions of DAP10 and DAP12 are sufficient to confer specific association with their partners. Although cross-linking of either DAP10- or DAP12-associated receptors has been shown to be sufficient to trigger NK cell-mediated cytotoxicity against Fc receptor-bearing cells, substantial synergy was observed in the induction of cytokine production when both receptors were engaged. Activation of the Syk/ZAP70 tyrosine kinases by the immunoreceptor tyrosine-based activation motif-containing DAP12 adaptor and of the phosphatidylinositol 3-kinase pathway by the YxNM-containing DAP10 adaptor may play an important role in the stimulation of NK cells and T cells.
        Cover page: Dap10 and Dap12 Form Distinct, but Functionally Cooperative, Receptor Complexes in Natural Killer CellsCreative Commons 'BY-NC-SA' version 4.0 license
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (1996)
        The killer cell inhibitory receptors (KIR) of human natural killer (NK) cells recognize human leukocyte antigen class I molecules and inhibit NK cell cytotoxicity through their interaction with protein tyrosine phosphatases (PTP). Here, we report that KIR recognition of class I ligands inhibits distal signaling events and ultimately NK cell cytotoxicity by blocking the association of an adaptor protein (pp36) with phospholipase C-gamma in NK cells. In addition, we demonstrate that pp36 can serve as a substrate in vitro for the KIR-associated PTP, PTP-1C (also called SHP-1), and that recognition of class I partially disrupts tyrosine phosphorylation of NK cell proteins, providing evidence for KIR-induced phosphatase activity.
          Cover page: Killer Cell Inhibitory Receptor Recognition of Human Leukocyte Antigen (HLA) Class I Blocks Formation of a pp36/PLC-γ Signaling Complex in Human Natural Killer (NK) CellsCreative Commons 'BY-NC-SA' version 4.0 license
          • Article
          • Peer Reviewed
          UC Santa Barbara Previously Published Works (2022)
          Abstract: The Pacific ocean-bottom seismometer (OBS) Research into Convecting Asthenosphere (ORCA) experiment deployed two 30-station seismic arrays between 2018 and 2020—a US contribution to the international PacificArray project. The “Young ORCA” array deployed on ∼40 Ma central Pacific seafloor had a ∼68% data recovery rate, whereas the “Old ORCA” array deployed on ∼120 Ma southwest Pacific seafloor had a ∼80% recovery rate. We detail here the seismic data quality, spectral characteristics, and engineering challenges of this experiment. We provide information to assist users of this dataset, including OBS orientations and tables of daily data quality for all channels. Preliminary analysis illustrates the utility of these data for surface- and body-wave seismic imaging.
            Cover page: The Pacific OBS Research into Convecting Asthenosphere (ORCA) ExperimentCreative Commons 'BY-ND' version 4.0 license
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2003)

            We report the cloning and functional characterization in the mouse and the rat of a novel natural killer (NK) cell receptor termed KLRE1. The receptor is a type 11 transmembrane protein with a COOH-terminal lectin-like domain, and constitutes a novel KLR family. Rat Klre1 was mapped to the NK gene complex. By Northern blot and flow cytometry using newly generated monoclonal antibodies, KLRE1 was shown to be expressed by NK cells and a subpopulation of CD3(+) cells, with pronounced interstrain variation. Western blot analysis indicated that KLRE1 can be expressed on the NK cell surface as a disulphide-linked dimer. The predicted proteins do not contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) or a positively charged amino acid in the transmembrane domain. However, in a redirected lysis assay, the presence of whole IgG, but not of F(ab')(2) fragments of a monoclonal anti-KLR-E1 antibody inhibited lysis of Fc-receptor bearing tumor target cells. Moreover, the tyrosine phosphatase SHP-1 was coimmunoprecipitated with KLRE1 from pervanadate-treated interleukin 2-activated NK cells. Together, our results indicate that KLRE1 may form a functional heterodimer with an as yet unidentified ITIM-bearing partner that recruits SHP-1 to generate an inhibitory receptor complex.

              Cover page: The lectin-like receptor KLRE1 inhibits natural killer cell cytotoxicity
              • Article
              • Peer Reviewed
              UC Santa Barbara Previously Published Works (2022)
                Cover page: The Pacific OBS Research into Convecting Asthenosphere (ORCA) Experiment
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2009)
                The activating natural killer (NK) cell receptor Ly49H recognizes the mouse cytomegalovirus (MCMV) m157 glycoprotein expressed on the surface of infected cells and is required for protection against MCMV. Although Ly49H has previously been shown to signal via DAP12, we now show that Ly49H must also associate with and signal via DAP10 for optimal function. In the absence of DAP12, DAP10 enables Ly49H-mediated killing of m157-bearing target cells, proliferation in response to MCMV infection, and partial protection against MCMV. DAP10-deficient Ly49H(+) NK cells, expressing only Ly49H-DAP12 receptor complexes, are partially impaired in their ability to proliferate during MCMV infection, display diminished ERK1/2 activation, produce less IFN-gamma upon Ly49H engagement, and demonstrate reduced control of MCMV infection. Deletion of both DAP10 and DAP12 completely abrogates Ly49H surface expression and control of MCMV infection. Thus, optimal NK cell-mediated immunity to MCMV depends on Ly49H signaling through both DAP10 and DAP12.
                  Cover page: Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infectionCreative Commons 'BY-NC-SA' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (1998)
                  Natural killer (NK) cells have been implicated in early immune responses against certain viruses, including cytomegalovirus (CMV). CMV causes downregulation of class I major histocompatibility complex (MHC) expression in infected cells; however, it has been proposed that a class I MHC homolog encoded by CMV, UL18, may act as a surrogate ligand to prevent NK cell lysis of CMV-infected cells. In this study, we examined the role of UL18 in NK cell recognition and lysis using fibroblasts infected with either wild-type or UL18 knockout CMV virus, and by using cell lines transfected with the UL18 gene. In both systems, the expression of UL18 resulted in the enhanced killing of target cells. We also show that the enhanced killing is due to both UL18-dependent and -independent mechanisms, and that the killer cell inhibitory receptors (KIRs) and CD94/NKG2A inhibitory receptors for MHC class I do not play a role in affecting susceptibility of CMV-infected fibroblasts to NK cell-mediated cytotoxicity.
                    Cover page: Modulation of Natural Killer Cell Cytotoxicity in Human Cytomegalovirus Infection: The Role of Endogenous Class I Major Histocompatibility Complex and a Viral Class I HomologCreative Commons 'BY-NC-SA' version 4.0 license
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2010)
                    The CD94 transmembrane-anchored glycoprotein forms disulfide-bonded heterodimers with the NKG2A subunit to form an inhibitory receptor or with the NKG2C or NKG2E subunits to assemble a receptor complex with activating DAP12 signaling proteins. CD94 receptors expressed on human and mouse NK cells and T cells have been proposed to be important in NK cell tolerance to self, play an important role in NK cell development, and contribute to NK cell-mediated immunity to certain infections including human cytomegalovirus. We generated a gene-targeted CD94-deficient mouse to understand the role of CD94 receptors in NK cell biology. CD94-deficient NK cells develop normally and efficiently kill NK cell-susceptible targets. Lack of these CD94 receptors does not alter control of mouse cytomegalovirus, lymphocytic choriomeningitis virus, vaccinia virus, or Listeria monocytogenes. Thus, the expression of CD94 and its associated NKG2A, NKG2C, and NKG2E subunits is dispensable for NK cell development, education, and many NK cell functions.
                      Cover page: Development and Function of CD94-Deficient Natural Killer CellsCreative Commons 'BY' version 4.0 license
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