A human homologue of the Drosophila Toll protein signals activation of adaptive immunity (original) (raw)

Nature volume 388, pages 394–397 (1997)Cite this article

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.

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Acknowledgements

We thank our colleagues for discussions; P. G. Waterbury for DNA sequencing; S.Ghosh and R. Voll for pB2XLuc plasmid and for helpful suggestions; and J. Flaxenberg for assistance. We acknowledge the Howard Hughes Medical Institute and the NIAID, NIH for support of this work.

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Authors and Affiliations

  1. *Section of Immunobiology, Yale University School of Medicine, New Haven, 06520-8011, Connecticut, USA
    Ruslan Medzhitov & Charles A. Janeway Jr
  2. Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, 06520-8011, Connecticut, USA
    Paula Preston-Hurlburt

Authors

  1. Ruslan Medzhitov
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  2. Paula Preston-Hurlburt
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  3. Charles A. Janeway Jr
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Correspondence toCharles A. Janeway Jr.

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Medzhitov, R., Preston-Hurlburt, P. & Janeway, C. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity.Nature 388, 394–397 (1997). https://doi.org/10.1038/41131

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