期刊
FEBS LETTERS
卷 591, 期 16, 页码 2406-2416出版社
WILEY
DOI: 10.1002/1873-3468.12768
关键词
epitope; inhibitory monoclonal antibody; leucine-rich repeat; lipopolysaccharide; MD-2; Toll-like receptor 4
资金
- JSPS KAKENHI [24790112]
- Takeda Science Foundation
- Ichiro Kanehara Foundation
- Research Foundation for Pharmaceutical Sciences
- Tokyo Biochemical Research Foundation
- Grants-in-Aid for Scientific Research [16K20909, 24790112] Funding Source: KAKEN
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 NF kappa B 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.
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