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  • DKFZ Publication Database  (2)
  • GENE  (2)
  • BONE-MARROW  (1)
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  • DKFZ Publication Database  (2)
  • 1
    Keywords: EXPRESSION ; IN-VITRO ; INVASION ; Germany ; VITRO ; GENE ; GENES ; PROTEIN ; PROTEINS ; COMPLEX ; COMPLEXES ; MECHANISM ; mechanisms ; ASSOCIATION ; MATURATION ; antibodies ; antibody ; CLEAVAGE ; ESCHERICHIA-COLI ; REGION ; PURIFICATION ; FRAGMENTS ; INTERACTS ; COMPLEX-FORMATION ; PRODUCTS ; MALARIA PARASITE ; function ; PRECURSOR ; MEROZOITE SURFACE PROTEIN-1 ; VACCINE CANDIDATE
    Abstract: Merozoites of the malaria parasite Plasmodium falciparum expose at their surface a large multiprotein complex, composed of proteolytically processed, noncovalently associated products of at least three genes, msp-1, msp-6, and msp-7. During invasion of erythrocytes, this complex is shed from the surface except for a small glycosylphosphatidylinositol-anchored portion originating from MSP-1. The proteolytic cleavage separating the C-terminal portion of MSP-1 is required for successful invasion. Little is known about the structure and function of the abundant and essential multipartite complex. Using heterologously produced MSP-1, MSP-6, and MSP-7 in precursor and with the exception of MSP-7 in processed form, we have studied in vitro the complex formation between the different proteins to identify the interaction partners within the complex. Both MSP-6(36) and MSP-7 bind only to MSP-1 subunits that are shed, but although MSP-636 contacts just subunit p38, MSP-7 interacts with p83, p30, and p38. The intact C-terminal region of MSP-6 is required for the association with p38 as well as for its multimerization into tetramers. Furthermore, our data suggest that only the processed form and not the precursor form of MSP-1 interacts with MSP-636. MSP-6-as well as MSP-7-specific rabbit antibodies inhibit parasite multiplication in vitro as shown previously for antibodies directed against MSP-1. Our findings raise interesting questions with regard to proteolysis-mediated mechanisms of maturation of the MSP-1-MSP-6-MSP-7 complex and to the mode by which antibodies directed against this complex interfere with parasite multiplication
    Type of Publication: Journal article published
    PubMed ID: 16940297
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  • 2
    Keywords: RECEPTOR ; CANCER ; CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; Germany ; IN-VIVO ; VIVO ; liver ; GENE ; GENE-EXPRESSION ; DIFFERENTIATION ; ACTIVATION ; CUTTING EDGE ; INFECTION ; INDUCTION ; DENDRITIC CELLS ; T-CELLS ; TOLERANCE ; bone marrow ; BONE-MARROW ; STIMULATION ; MOUSE ; DELIVERY ; CLONAL EXPANSION ; VIRAL-INFECTION ; CROSS-PRESENTATION ; endothelial cells ; EFFECTOR FUNCTION ; RIG-I ; T cell immunity ; HEPATITIS-B VIRUS ; MURINE CYTOMEGALOVIRUS-INFECTION ; TOLEROGENIC DENDRITIC CELLS
    Abstract: BACKGROUND & AIMS: Dendritic cell activation through ligation of pattern recognition receptors leading to full functional maturation causes induction of CD8(+) T-cell immunity through increased delivery of costimulatory signals instead of tolerance. Here we investigate whether organ-resident antigen-presenting cells, such as liver sinusoidal endothelial cells (LSECs), also switch from tolerogenic to immunogenic CD8(+) T-cell activation upon such stimulation. METHODS: Murine LSECs were isolated by immunomagnetic separation and analyzed for functional maturation upon triggering pattern recognition receptors or viral infection employing gene expression analysis and T cell coculture assays. In vivo relevance of the findings was confirmed with bone-marrow chimeric animals. RESULTS: LSECs expressed numerous pattern recognition receptors that allowed for sentinel function, but ligand-induced activation of these receptors was not sufficient to overcome tolerance induction of CD8(+) T cells. Importantly, viral infection with murine cytomegalovirus caused functional maturation of antigen-presenting LSECs and was sufficient to promote antigen-specific differentiation into effector CD8(+) T cells in the absence of dendritic cells and independent of CD80/86. CONCLUSIONS: These results shed new light on the generation of organ-specific immunity and may contribute to overcoming tolerance in relevant situations, such as cancer
    Type of Publication: Journal article published
    PubMed ID: 19737567
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