Down modulation of human TLR3 function by a monoclonal antibody

Area of Science:

• Immunology
• Molecular Biology

Background:

• Toll-like receptors (TLRs) are crucial pattern-recognition receptors in the innate immune system.
• Toll-like receptor 3 (TLR3) recognizes various ligands, including viral dsRNA and synthetic analogs like poly(I:C).

Purpose of the Study:

• To generate and characterize a novel monoclonal antibody (mAb CNTO2424) targeting the extracellular domain of human TLR3.
• To investigate the functional impact of mAb CNTO2424 on TLR3-mediated signaling and cytokine production.

Main Methods:

• Generation of a conformation-dependent monoclonal antibody (mAb CNTO2424) against human TLR3.
• Assessment of mAb CNTO2424's effect on poly(I:C)-induced cytokine production (IL-6, IL-8, MCP-1, RANTES, IP-10) in human lung epithelial cells.
• Analysis of TLR3-dependent signaling pathways (NF-kappaB, IRF-3/ISRE, p38 MAPK) interference by mAb CNTO2424.

Main Results:

• mAb CNTO2424 recognizes the extracellular domain of human TLR3 in a conformation-dependent manner.
• CNTO2424 significantly down-regulates poly(I:C)-induced production of key inflammatory cytokines and chemokines.
• The antibody effectively interferes with established TLR3 signaling cascades, including NF-kappaB, IRF-3/ISRE, and p38 MAPK pathways.

Conclusions:

• The development of mAb CNTO2424 provides a valuable neutralizing tool for studying TLR3 function.
• This antibody can elucidate TLR3 signaling mechanisms and potential cross-talk with other molecular pathways in innate immunity.