Anti-hTLR4 Neutralizing mAb

Human TLR4 Neutralization - Monoclonal Mouse IgG1

Neutralizing activity of Anti-hTLR4-IgG

Anti-hTLR4-IgG (clone W7C11) is a neutralizing monoclonal antibody specific for human Toll-like receptor 4 (hTLR4, CD284). It has been produced in hybridoma cells and purified by affinity chromatography. This antibody has been selected for its ability to efficiently neutralize the biological activity of hTLR4.

TLR4 primarily recognizes and is activated by lipopolysaccharide  (LPS) and its toxic moiety Lipid A [1].  At the cell surface, activation of TLR4 initiates the MyD88-dependent pathway, leading to the activation of NF-κB and the production of a pro-inflammatory response [2].

More details

Key features:

• Reacts with human TLR4
• Provided azide-free
• Each lot is functionally tested

References

1. Cochet, F. et al., 2017. The Role of Carbohydrates in the Lipopolysaccharide (LPS)/Toll-Like Receptor 4 (TLR4) Signalling. Int J Mol Sci 18
2. Kuzmich, N.N. et al., 2017. TLR4 Signaling Pathway Modulators as Potential Therapeutics in Inflammation and Sepsis. Vaccines (Basel) 5.

Specifications

Target: Human TLR4

Specificity: No cross-reactivity with murine TLR4

Clonality: Monoclonal antibody

Clone: W7C11

Isotype: Mouse IgG1, kappa

Control: Mouse Control IgG1

Source: Hybridoma cells

Formulation: 0.2 µm filtered solution in a sodium phosphate buffer with saccharose, glycine, and stabilizing agents

Applications: Neutralizing human TLR4-induced cellular activation

Quality control:

• This product has been validated for neutralization using cellular assays.
• The absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ TLR2 and HEK‑Blue™ TLR4 cells.

Contents

• 2 x 100 µg of purified Anti-hTLR4 IgG monoclonal antibody, provided lyophilized and azide-free.

Product is shipped at room temperature.

Upon receipt, store lyophilized Anti-hTLR4-IgG at -20°C.

Details

Toll-like receptors (TLRs) play a critical role in early innate immunity to invading pathogens by sensing microorganisms. These evolutionarily conserved receptors recognize highly conserved structural motifs only expressed by microbial pathogens, called pathogen-associated microbial patterns (PAMPs). Stimulation of TLRs by PAMPs initiates a signaling cascade leading to the secretion of proinflammatory cytokines following NF-κB activation. To date ten human and twelve murine TLRs have been characterized, TLR1 to TLR10 in humans, and TLR1 to TLR9, TLR11, TLR12, and TLR13 in mice, the homolog of TLR10 being a pseudogene.

TLR4, the first human TLR identified, is the receptor for Gram-negative lipopolysaccharide (LPS). The TLR4 gene was shown to be mutated in C3H/HeJ and C57BL/10ScCr mice, both of which are low responders to LPS [1]. However, TLR4 alone is not sufficient to confer LPS responsiveness. TLR4 requires MD-2, a secreted molecule, to functionally interact with LPS [2]. Furthermore, a third protein, called CD14, was shown to participate in LPS signaling, leading to NF-κB translocation. This signaling is mediated through several adaptor proteins: MyD88 TIRAP/Mal [3], TRIF/TICAM1, and TRAM/TICAM2 [4].

1. Poltorak A. et al., 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science, 282(5396):2085-8.
2. Shimazu R. et al., 1999. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med, 189(11):1777-82.
3. Horng T. GM. Barton, & R. Medzhitov, 2001. TIRAP: an adapter molecule in the Toll signaling pathway. Nat Immunol, 2(9):835-41.
4. Fitzgerald KA. et al., 2003. LPS-TLR4 Signaling to IRF-3/7 and NF-{kappa}B Involves the Toll Adapters TRAM and TRIF. J Exp Med. 198(7):1043-1055.