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

    DOI

    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
    56 adaptive immune responses
    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
    80 human homologue
    81 human interleukin
    82 human toll
    83 immune response
    84 immune system
    85 immunity
    86 induction
    87 infection
    88 inflammatory cytokines IL-1
    89 initial induction
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    91 interleukin
    92 leucine-rich repeat domain
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    96 mutants
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