@article{da08481ffc6641b691318c3720ab72e6,
title = "Leucine-rich repeat 2 of human Toll-like receptor 4 contains the binding site for inhibitory monoclonal antibodies",
abstract = "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 Phe75, Ser76 and Pro79 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.",
keywords = "Epitope, Inhibitory monoclonal antibody, Lipopolysaccharide, MD-2, Toll-like receptor 4",
author = "Hiroki Tsukamoto and Ippo Ukai and Yuki Yamagata and Shino Takeuchi and Kanae Kubota and Sao Kozakai and Naoto Suzuki and Masao Kimoto and Yoshihisa Tomioka",
note = "Funding Information: This work was supported in part by JSPS KAKENHI Grant numbers 24790112 and 26460058 (HT), a Grant provided by The Ichiro Kanehara Foundation (HT), the Research Foundation for Pharmaceutical Sciences (HT), and the Tokyo Biochemical Research Foundation (HT). We thank Drs. Akira and Miyake for providing us with TLR4 -deficient mice and Ba/F3-transfected cells, respectively. Publisher Copyright: {\textcopyright} 2015 Federation of European Biochemical Societies.",
year = "2015",
month = dec,
day = "21",
doi = "10.1016/j.febslet.2015.11.018",
language = "English",
volume = "589",
pages = "3893--3898",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "24",
}