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

  title={A human homologue of the Drosophila Toll protein signals activation of adaptive immunity},
  author={Ruslan Medzhitov and Paula Preston-Hurlburt and Charles A. Jr Janeway},
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… 

A family of human receptors structurally related to Drosophila Toll.

This work reports the molecular cloning of a class of putative human receptors with a protein architecture that is similar to Drosophila Toll in both intra- and extracellular segments and indicates markedly different patterns of expression for the human TLRs.

The Toll receptor family

Tolllike receptors (TLR) structure, ligand recognition, signal transduction, and expression pattern are reviewed, and speculation about their functional role is speculated.

Toll-related receptors and the control of antimicrobial peptide expression in Drosophila.

Six additional Toll-related genes (Toll-3 to Toll-8) are described in Drosophila in addition to 18-wheeler, finding that only Toll and Toll-5 can activate the drosomycin promoter in transfected cells, thus demonstrating specificity at the level of the Toll/IL-1R homology domain.

Homology Modeling of Toll-Like Receptor Ligand-Binding Domains

This dissertation predicted potential ligand-binding residues and possible configurations of the receptor-ligand complex using a combined procedure and modeled the cytoplasmic TIR domains of TLR4 and 7, the TLR adaptor protein MyD88 (myeloid differentiation primary response protein 88) and theTLR inhibitor SIGIRR to investigate the structural mechanism ofTLR negative regulation.

Toll receptors: an expanding role in our understanding of human disease

Toll receptor proteins in Drosophila are involved in establishing the dorsal‐ventral axis in embryogenesis as well as participating in the innate immune response to invading pathogens, and a better understanding of this response may provide improved therapeutic modalities in the treatment of bacterial and fungal sepsis.

Toll-like Receptors: Implication in Human Disease

The recently identified receptors of the Toll family appear to have a major role in the induction of immune and inflammatory responses, and two discoveries support this role.



Signals from the IL-1 receptor homolog, Toll, can activate an immune response in a Drosophila hemocyte cell line.

The endogenous Toll gene is expressed in mbn-2 cells, indicating that this gene may normally play a role in Drosophila blood cells, and Toll10B was found to increase CecA1 transcription, as detected with a cotransfected CecA 1-lacZ reporter gene construct.

A conserved signaling pathway: the Drosophila toll-dorsal pathway.

The Toll-Dorsal pathway in Drosophila and the interleukin-1 receptor (IL-1R)-NF-kappa B pathway in mammals are homologous signal transduction pathways that mediate several different biological

Molecular genetics of Drosophila immunity.

Ventralization of the Drosophila embryo by deletion of extracellular leucine-rich repeats in the Toll protein.

The view that Toll is a receptor whose extracellular domain regulates the intrinsic signaling activity of its cytoplasmic domain is supported.

A conserved signal transduction pathway regulating the activity of the rel-like proteins dorsal and NF-kappa B.

The establishment of dorsoventral polarity in the Drosophila embryo and its relationship to a mammalian signal transduction pathway is considered.

Dominant and recessive mutations define functional domains of Toll, a transmembrane protein required for dorsal-ventral polarity in the Drosophila embryo.

Three of five recessive loss-of-function alleles of Toll are caused by point mutations in the region of the cytoplasmic domain of Toll that is similar to the mammalian interleukin-1 receptor, supporting the hypothesis that Toll acts as a signal-transducing receptor.

RP105, a novel B cell surface molecule implicated in B cell activation, is a member of the leucine-rich repeat protein family.

It is demonstrated that RP105 is a novel member of the leucine-rich repeat protein family, and the first member that is specifically expressed on B cells.