TRIF (F6K4E) Rabbit mAb #16809

Members of the Toll-like receptor (TLR) family, named for the closely related Toll receptor in Drosophila, play a pivotal role in innate immune responses (1-4). TLRs recognize conserved motifs found in various pathogens and mediate defense responses (5-7). Triggering of the TLR pathway leads to the activation of NF-κB and subsequent regulation of immune and inflammatory genes (4). The TLRs and members of the IL-1 receptor family share a conserved stretch of approximately 200 amino acids known as the Toll/Interleukin-1 receptor (TIR) domain (1). Upon activation, TLRs associate with a number of cytoplasmic adapter proteins containing TIR domains, including myeloid differentiation factor 88 (MyD88), MyD88-adapter-like/TIR-associated protein (MAL/TIRAP), TIR domain-containing adapter-inducing IFN-β (TRIF), and Toll-receptor-associated molecule (TRAM) (8-10). This association leads to the recruitment and activation of IRAK1 and IRAK4, which form a complex with TRAF6 to activate TAK1 and IKK (8,11-14). Activation of IKK leads to the degradation of IκB, which normally maintains NF-κB in an inactive state by sequestering it in the cytoplasm.

TRIF, also known as TIR domain-containing adapter molecule 1 (TICAM-1), is a TIR domain adapter protein described to activate NF-κB and IRF3 and trigger IFN-β production (15,16). Studies using dominant negative forms of TRIF and siRNA targeting TRIF show that TRIF functions downstream of TLR3 and TLR4 in response to dsRNA and LPS, respectively (15-17). TRIF recruits TRAF6-TAK1-TAB2 to the receptor complex, which leads to NF-κB activation (18). In addition, TRIF can trigger signaling that leads to the induction of apoptosis (19).