Your browser version may not work well with NCBI's Web applications. More information here...
1: Nature. 1997 Jul 24;388(6640):394-7.
Related Articles, Links
Click here to read
Comment in:
A human homologue of the Drosophila Toll protein signals activation of adaptive immunity.

Medzhitov R, Preston-Hurlburt P, Janeway CA Jr.

Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.

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:
PMID: 9237759 [PubMed - indexed for MEDLINE]