TY - JOUR
T1 - Preparation and characterization of agonistic monoclonal antibodies against toll-like receptor 4-MD-2 complex
AU - Bahrun, Uleng
AU - Kimoto, Masao
AU - Tsukamoto, Hiroki
AU - Tsuneyoshi, Naoko
AU - Kohara, Jun
AU - Fukudome, Kenji
PY - 2007/12/1
Y1 - 2007/12/1
N2 - 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.
AB - 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.
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U2 - 10.1089/hyb.2007.0523
DO - 10.1089/hyb.2007.0523
M3 - Article
C2 - 18158784
AN - SCOPUS:37549067669
VL - 26
SP - 393
EP - 399
JO - Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
JF - Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
SN - 2167-9436
IS - 6
ER -