A Human Homologue of the Drosophila Toll Protein Signals Activation of Adaptive Immunity

Nature. 1997 Jul 24;388(6640):394-7. doi: 10.1038/41131.

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 vertebrates. 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 Drosophila. 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-kappaB pathway. We show that a constitutively active mutant of human Toll transfected into human cell lines can induce the activation of NF-kappaB and the expression of NF-kappaB-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • B7-1 Antigen / biosynthesis
  • B7-1 Antigen / genetics
  • Cell Line
  • Cloning, Molecular
  • Drosophila
  • Drosophila Proteins*
  • Humans
  • Immunity*
  • Insect Proteins / immunology*
  • Interleukins / biosynthesis
  • Interleukins / genetics
  • Jurkat Cells
  • Membrane Glycoproteins / immunology*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Mutation
  • NF-kappa B / metabolism
  • Receptors, Cell Surface*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • T-Lymphocytes / immunology
  • Toll-Like Receptors
  • Transfection

Substances

  • B7-1 Antigen
  • Drosophila Proteins
  • Insect Proteins
  • Interleukins
  • Membrane Glycoproteins
  • Membrane Proteins
  • NF-kappa B
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Recombinant Fusion Proteins
  • Tl protein, Drosophila
  • Toll-Like Receptors

Associated data

  • GENBANK/U93091