Down modulation of human TLR3 function by a monoclonal antibody

Cell Immunol. 2007 Aug;248(2):103-14. doi: 10.1016/j.cellimm.2007.10.002. Epub 2007 Nov 28.

Abstract

Toll-like receptors are a family of pattern-recognition receptors that contribute to the innate immune response. Toll-like receptor 3 (TLR3) signals in response to foreign, endogenous and synthetic ligands including viral dsRNA, bacterial RNA, mitochondrial RNA, endogenous necrotic cell mRNA and the synthetic dsRNA analog, poly(I:C). We have generated a monoclonal antibody (mAb CNTO2424) that recognizes the extracellular domain (ECD) of human TLR3 in a conformation-dependent manner. CNTO2424 down-regulates poly(I:C)-induced production of IL-6, IL-8, MCP-1, RANTES, and IP-10 in human lung epithelial cells. In addition, mAb CNTO2424 was able to interfere with the known TLR3-dependent signaling pathways, namely NF-kappaB, IRF-3/ISRE, and p38 MAPK. The generation of this neutralizing anti-TLR3 mAb provides a unique tool to better understand TLR3 signaling and potential cross-talk between TLR3 and other molecules.

MeSH terms

  • Animals
  • Antibodies, Blocking / metabolism
  • Antibodies, Monoclonal* / metabolism
  • Binding Sites, Antibody
  • Cell Line
  • Cell Line, Transformed
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Pilot Projects
  • Toll-Like Receptor 3 / antagonists & inhibitors*
  • Toll-Like Receptor 3 / immunology*
  • Toll-Like Receptor 3 / metabolism

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • TLR3 protein, human
  • Toll-Like Receptor 3