TIR domain-containing adaptors define the specificity of TLR signaling

Mol Immunol. 2004 Feb;40(12):861-8. doi: 10.1016/j.molimm.2003.10.006.


The concept that Toll-like receptors (TLRs) recognize specific molecular patterns in various pathogens has been established. In signal transduction via TLRs, MyD88, which harbors a Toll/IL-1 receptor (TIR)-domain and a death domain, has been shown to link between TLRs and MyD88-dependent downstream events leading to proinflammatory cytokine production and splenocyte proliferation. However, recent studies using MyD88-deficient mice have revealed that some TLRs possess a MyD88-independent pathway, which is represented by interferon (IFN)-beta production induced by LPS stimulation. This indicates that additional signaling molecules other than MyD88 exist in the TLR signaling pathway. Indeed, two additional TIR domain-containing adaptors, TIRAP/Mal and TRIF, have recently been identified. Both define the specific biological responses of each TLR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport / genetics*
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Antigens, Differentiation / metabolism*
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Knockout
  • Myeloid Differentiation Factor 88
  • Protein Structure, Tertiary
  • Receptors, Cell Surface / metabolism*
  • Receptors, Immunologic / metabolism*
  • Receptors, Interleukin-1 / genetics*
  • Receptors, Interleukin-1 / metabolism
  • Signal Transduction / physiology*
  • Toll-Like Receptors


  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Antigens, Differentiation
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Receptors, Interleukin-1
  • TICAM-1 protein, mouse
  • TIRAP protein, mouse
  • Toll-Like Receptors