First Author | Tsukamoto H | Year | 2017 |
Journal | FEBS Lett | Volume | 591 |
Issue | 16 | Pages | 2406-2416 |
PubMed ID | 28741733 | Mgi Jnum | J:254139 |
Mgi Id | MGI:6099575 | Doi | 10.1002/1873-3468.12768 |
Citation | Tsukamoto H, et al. (2017) An inhibitory epitope of human Toll-like receptor 4 resides on leucine-rich repeat 13 and is recognized by a monoclonal antibody. FEBS Lett 591(16):2406-2416 |
abstractText | Lipopolysaccharide (LPS)-induced activation of Toll-like receptor 4 (TLR4) elicits the innate immune response and can trigger septic shock if excessive. Two antibodies (HT4 and HT52) inhibit LPS-induced human TLR4 activation via novel LPS binding-independent mechanisms. The HT52 epitope resides on leucine-rich repeat 2 (LRR2) and is a feature of many inhibitory antibodies; antigen specificity of HT4 does not reside in LRR2. Here, we identified an HT4 epitope on LRR13 located close to the TLR4 dimerization interface that plays a role in NFkappaB activation. HT4 and HT52 mutually enhanced TLR4 inhibition. LRR13 is a novel inhibitory epitope and may be useful for developing anti-TLR4 antibodies. Combination therapy with LRR2 and LRR13 may effectively inhibit TLR4 activation. |