An inhibitory epitope of human Toll-like receptor 4 resides on leucine-rich repeat 13 and is recognized by a monoclonal antibody.

Hiroki Tsukamoto, Yuki Yamagata, Ippo Ukai, Shino Takeuchi, Misaki Okubo, Yohei Kobayashi, Sao Kozakai, Kanae Kubota, Muneo Mumasaki, Yoshitomi Kanemitsu, Yotaro Matsumoto, Yoshihisa Tomioka

FEBS letters 2017 Aug

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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 NFκB 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. © 2017 Federation of European Biochemical Societies.

Citation

Hiroki Tsukamoto, Yuki Yamagata, Ippo Ukai, Shino Takeuchi, Misaki Okubo, Yohei Kobayashi, Sao Kozakai, Kanae Kubota, Muneo Mumasaki, Yoshitomi Kanemitsu, Yotaro Matsumoto, Yoshihisa Tomioka. An inhibitory epitope of human Toll-like receptor 4 resides on leucine-rich repeat 13 and is recognized by a monoclonal antibody. FEBS letters. 2017 Aug;591(16):2406-2416