Leucine-rich repeat 2 of human Toll-like receptor 4 contains the binding site for inhibitory monoclonal antibodies

Hiroki Tsukamoto, Ippo Ukai, Yuki Yamagata, Shino Takeuchi, Kanae Kubota, Sao Kozakai, Naoto Suzuki, Masao Kimoto, Yoshihisa Tomioka

研究成果: Article査読

6 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)3893-3898
ページ数6
ジャーナルFEBS Letters
589
24
DOI
出版ステータスPublished - 2015 12 21

ASJC Scopus subject areas

  • 生物理学
  • 構造生物学
  • 生化学
  • 分子生物学
  • 遺伝学
  • 細胞生物学

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