Immunology Discovery Department, Centocor Research & Development, Inc., Radnor, PA, USA.
Cell Immunol. 2011;267(1):9-16. doi: 10.1016/j.cellimm.2010.10.008. Epub 2010 Nov 2.
Toll-like receptor 3 (TLR3) binds and signals in response to dsRNA and poly(I:C), a synthetic double stranded RNA analog. Activation of TLR3 triggers innate responses that may play a protective or detrimental role in viral infections or in immune-mediated inflammatory diseases through amplification of inflammation. Two monoclonal antibodies, CNTO4685 (rat anti-mouse TLR3) and CNTO5429 (CDRs from CNTO4685 grafted onto a mouse IgG1 scaffold) were generated and characterized. These mAbs bind the extracellular domain of mouse TLR3, inhibit poly(I:C)-induced activation of HEK293T cells transfected with mTLR3, and reduce poly(I:C)-induced production of CCL2 and CXCL10 by primary mouse embryonic fibroblasts. CNTO5429 decreased serum IL-6 and TNFα levels post-intraperitoneal poly(I:C) administration, demonstrating in vivo activity. In summary, specific anti-mTLR3 mAbs have been generated to assess TLR3 antagonism in mouse models of inflammation.
Toll 样受体 3（TLR3）结合并响应双链 RNA（dsRNA）和聚肌苷酸：胞苷酸（poly(I:C)），一种合成的双链 RNA 类似物，发生信号转导。TLR3 的激活引发先天反应，这些反应可能通过炎症放大在病毒感染或免疫介导的炎症性疾病中发挥保护或有害作用。生成并表征了两种单克隆抗体，CNTO4685（抗鼠 TLR3 的大鼠单克隆抗体）和 CNTO5429（源自 CNTO4685 的 CDR 移植到小鼠 IgG1 支架上）。这些 mAb 结合小鼠 TLR3 的细胞外结构域，抑制转染 mTLR3 的 HEK293T 细胞中 poly(I:C)诱导的激活，并减少原代小鼠胚胎成纤维细胞中 poly(I:C)诱导的 CCL2 和 CXCL10 的产生。CNTO5429 降低了腹腔内 poly(I:C)给药后血清中 IL-6 和 TNFα 的水平，证明了体内活性。总之，已经生成了特异性抗 mTLR3 mAb 来评估 TLR3 拮抗剂在炎症小鼠模型中的作用。
