A human homologue of the Drosophila Toll protein signals activation of adaptive immunity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1997-07

AUTHORS

Ruslan Medzhitov, Paula Preston-Hurlburt, Charles A. Janeway

ABSTRACT

Induction of the adaptive immune response depends on the expression of co-stimulatory molecules and cytokines by antigen-presenting cells. The mechanisms that control the initial induction of these signals upon infection are poorly understood. It has been proposed that their expression is controlled by the non-clonal, or innate, component of immunity that preceded in evolution the development of an adaptive immune system in vertebrates1. We report here the cloning and characterization of a human homologue of the Drosophila toll protein (Toll) which has been shown to induce the innate immune response in adult Drosophila2,3,4. Like Drosophila Toll, human Toll is a type I transmembrane protein with an extracellular domain consisting of a leucine-rich repeat (LRR) domain, and a cytoplasmic domain homologous to the cytoplasmic domain of the human interleukin (IL)-1 receptor. Both Drosophila Toll and the IL-1 receptor are known to signal through the NF-κB pathway5,6,7. We show that a constitutively active mutant of human Toll transfected into human cell lines can induce the activation of NF-κB and the expression of NF-κB-controlled genes for the inflammatory cytokines IL-1, IL-6 and IL-8, as well as the expression of the co-stimulatory molecule B7.1, which is required for the activation of naive T cells. More... »

PAGES

394-397

References to SciGraph publications

  • 1991-05. Drosophila Toll and IL-1 receptor in NATURE
  • 1994-02-01. Issues in searching molecular sequence databases in NATURE GENETICS
  • 1994-01. Ancient relationships in NATURE
  • Journal

    TITLE

    Nature

    ISSUE

    6640

    VOLUME

    388

    Clinical Trials linked to this publication

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/41131

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    http://dx.doi.org/10.1038/41131

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1048300852

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/9237759


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    37 schema:description Induction of the adaptive immune response depends on the expression of co-stimulatory molecules and cytokines by antigen-presenting cells. The mechanisms that control the initial induction of these signals upon infection are poorly understood. It has been proposed that their expression is controlled by the non-clonal, or innate, component of immunity that preceded in evolution the development of an adaptive immune system in vertebrates1. We report here the cloning and characterization of a human homologue of the Drosophila toll protein (Toll) which has been shown to induce the innate immune response in adult Drosophila2,3,4. Like Drosophila Toll, human Toll is a type I transmembrane protein with an extracellular domain consisting of a leucine-rich repeat (LRR) domain, and a cytoplasmic domain homologous to the cytoplasmic domain of the human interleukin (IL)-1 receptor. Both Drosophila Toll and the IL-1 receptor are known to signal through the NF-κB pathway5,6,7. We show that a constitutively active mutant of human Toll transfected into human cell lines can induce the activation of NF-κB and the expression of NF-κB-controlled genes for the inflammatory cytokines IL-1, IL-6 and IL-8, as well as the expression of the co-stimulatory molecule B7.1, which is required for the activation of naive T cells.
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    44 Drosophila Toll
    45 Drosophila Toll protein
    46 IL-1
    47 IL-1 receptor
    48 IL-6
    49 IL-8
    50 NF-κB
    51 NF-κB-controlled genes
    52 T cells
    53 Toll protein
    54 activation
    55 active mutant
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    57 adaptive immune system
    58 adaptive immunity
    59 adults
    60 antigen-presenting cells
    61 cell lines
    62 cells
    63 characterization
    64 cloning
    65 co-stimulatory molecules
    66 co-stimulatory molecules B7.1
    67 components
    68 components of immunity
    69 cytokines
    70 cytokines IL-1
    71 cytoplasmic domain
    72 development
    73 domain
    74 evolution
    75 expression
    76 extracellular domain
    77 genes
    78 homologues
    79 human cell lines
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    81 human interleukin
    82 human toll
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    85 immunity
    86 induction
    87 infection
    88 inflammatory cytokines IL-1
    89 initial induction
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