期刊
FEBS LETTERS
卷 589, 期 24, 页码 3893-3898出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2015.11.018
关键词
Toll-like receptor 4; MD-2; Inhibitory monoclonal antibody; Lipopolysaccharide; Epitope
资金
- JSPS KAKENHI [24790112, 26460058]
- Ichiro Kanehara Foundation
- Research Foundation for Pharmaceutical Sciences
- Tokyo Biochemical Research Foundation
- Grants-in-Aid for Scientific Research [24790112, 26460058] Funding Source: KAKEN
Excessive activation of Toll-like receptor 4 (TLR4)/MD-2 by lipopolysaccharide (LPS) causes septic shock. We previously produced an inhibitory antibody, HT52, against LPS-induced human TLR4 activation independently of LPS binding of MD-2. Consistent with the hypothesis that HT52 recognizes the epitopes inherent to inhibitory antibodies, we generated an HT52-crossblockable antibody and revealed the relationship between its inhibitory activity and the anti-TLR4 antibody epitope. Leucine-rich repeat 2 was identified as an inhibitory epitope, and Phe(75), Ser(76) and Pro(79) as antigenic determinants. These findings provide a way to design therapeutic antibodies targeted to TLR4 that are distinct from LPS analog antagonists targeting MD-2. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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