Preparation and characterization of agonistic monoclonal antibodies against toll-like receptor 4-MD-2 complex

Uleng Bahrun, Masao Kimoto, Hiroki Tsukamoto, Naoko Tsuneyoshi, Jun Kohara, Kenji Fukudome

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Ligands for toll-like receptors (TLR) are known to induce a variety of immune responses. Selective induction of desirable responses would be important for the treatment of individual diseases with various pathogenesis. For this purpose, we established six MAbs against the TLR4/MD-2 complex (UT MAbs) from TLR4-/- mice or MD-2-/- mice. Three MAbs (UT12, 18, and 22) induced NF-κB activation and production of pro-inflammatory cytokines, but the other three (UT15, 41, and 49) did not induce such cell responses. Unlike lipopolysaccharide (LPS), agonistic UT MAbs did not require serum components for the functions. UT41 and UT49 recognized TLR4 in the absence of MD-2. On the other hand, the other four MAbs reacted to the TLR4/MD-2 complex, but not to solo TLR4. Agonistic UT MAbs shared the epitopes, but non-agonistic UT15 reacted to distinct epitope on the complex. UT MAbs appear to be useful analyzing the molecular mechanism of TLR signaling and will contribute to the development of novel immunotherapies.

Original languageEnglish
Pages (from-to)393-399
Number of pages7
JournalHybridoma
Volume26
Issue number6
DOIs
Publication statusPublished - 2007 Dec 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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