Antigen families

Toll-like receptors/Adaptor proteins


The Toll-like receptors (TLRs) represent the prototype pattern recognition receptors (PRRs) characterized by a high degree of evolutionary conservation. Since the discovery of Drosophila “Toll”, a number of homologous TLRs have been identified in mammals (1). 10 genes encoding TLRs have been identified in humans. In the mouse, 13 such genes are described, although the murine equivalent of human Tlr10 is a pseudogene.
TLRs are type-I proteins featuring a leucine-rich repeat (LRR) extracellular domain, a short transmembrane region, and an intracellular Toll-IL1-R (TIR) domain. In humans, TLRs can be grouped into the TLR1, -2, -6, -10, and the TLR7 (mAb DENDRITICS), -8 (mAb DENDRITICS), -9 subfamilies, while TLR3 (mAb DENDRITICS), -4, and -5 appear phylogenetically more isolated. The LRR domain of the TLRs detect “pathogen associated molecular patterns” (PAMPs) that represent specific signatures of microorganisms. Such recognition events provide the basis for alerting the immune system to the presence of danger, in order to mount the most appropriate response (2, 3).
In contrast to the CLRs, TLR-ligands belong to widely different classes of molecules. While many TLR-ligands are of microbial origin (eg lipoproteins, lipopeptides, LPS, zymosan, flagellin, RNA, DNA), endogenous ligands are also common (eg heat-shock proteins, complexed RNA, complexed DNA) (4). In addition, it is of note that a number of synthetic ligands (eg imidazoquinolines, CpG-oligodeoxynucleotides) show therapeutic promise as agonists or antagonists of TLR functions (5, 6, 7).
The latter point emphasizes the importance of extending current knowledge on the cellular distribution and function of the various TLRs in steady-state and disease. As sensors of the immune system, DCs are well-equipped with a variety of TLRs (8).
Human conventional DCs express all TLRs with the exception of TLR9. By contrast, plasmacytoid DCs (pDCs) express TLR9, in addition to TLR7 (mAb DENDRITICS). Signaling via TLRs results in a multitude of coordinated events, including cellular activation, cytokine production and migration, that imprint the type of response initiated by the DCs. One of the features of conventional DCs upon TLR engagement is their capacity to express pro-inflammatory cytokines such as IL-12, leading to production of IFN-? and subsequent Th1-type adaptive immunity (9). As a reflection of their specialization in innate antiviral immunity, pDCs respond to TLR-7 (mAb DENDRITICS) and -9 ligands by producing high amounts of IFN-alpha/beta (10). Notably however, unlike the CLR pattern recognition receptors, TLRs appear to lack the capacity to internalize bound ligands and thus do not function in antigen capture by DCs. Triggering of the TLRs upon ligand binding results in the recruitment of adaptor molecules to the intracellular TIR domains. A central adaptor is MyD88 which is indispensable for signaling via the TLR9 and -2 subfamilies, as well as via TLR5. As a consequence of these early events, IL-1 receptor-associated kinase 4 (IRAK4) (mAb DENDRITICS) becomes recruited, and represents a link to the activation of two downstream pathways: the NF-kappa B pathway and the MAP-kinase pathway. Other adaptor molecules to the TLR TIR domains also exist. These include TIRAP/Mal (heterodimerizing with MyD88 (mAb DENDRITICS) for TLR2 and -4 signaling), TRIF/TICAM (in MyD88-independent signaling via TLR3 and -4), and TRAM/TICAM-2 (in TRIF-dependent signaling via TLR4) (11, 12). TLRs are also expressed by non-immune cells. Further expanding the field of TLR research, it has recently been shown that a synthetic agonist of TLR3 (mAb DENDRITICS) induces apoptotic death of human breast cancer cells (13).

References
1. Takeda K, Kaisho T, Akira S., Toll-like receptors, 2003 Ann Rev Immunol 21: 335-376
2. Kawai T, Akira S., Pathogen recognition with Toll-like receptors, 2005 Curr Opin Immunol 17: 338-44
3. Pasare C, Medzhitov R., Toll-like receptors: linking innate and adaptive immunity, 2004 Microbes Infect 6: 1382-1387.
4. Boule MW, Broughton C, Mackay F, Akira S, Marshak-Rothstein A, Rifkin IR., Toll-like receptor 9-dependent and -independent dendritic cell activation by chromatin-immunoglobulin G complexes, 2004 J Exp Med 199: 1631-1640
5. Akira S, Hemmi H.. Recognition of pathogen-associated molecular patterns by TLR family, 2003 Immunol Lett 85: 85-92
6. Zuany-Amorim C, Hastewell J, Walker C.. Toll-like receptors as potential therapeutic targets for multiple diseases, 2002 Nat Rev Drug Discovery 1: 797-807
7. Gupta AK, Cherman AM, Tyring SK. Viral and nonviral uses of imiquimod: a review, 2004 J Cutan Med Surg 8: 338-52
8. Reis e Sousa C.. Toll-like receptors and dendritic cells: for whom the bug tolls, 2004 Semin Immunol 16: 27-34.
9. Trinchieri G.. Interleukin-12 and the regulation of innate resistance and adaptive immunity, 2003 Nat Rev Immunol 3: 133-46.
10. Hochrein H, O'Keeffe M, Wagner H.. Human and mouse plasmacytoid dendritic cells, 2002 Hum Immunol 63: 1103-1110.
11. Kawai T, Akira S.. TLR signaling, 2006 Cell Death Differ 13: 816-825
12. McGettrick AF, O'Neill LA.. The expanding family of MyD88-like adaptors in Toll-like receptor signal transduction, 2004 Mol Immunol 41: 577-582. 13.Salaun B, Coste I, Rissoan MC, Lebecque SJ, Renno T. TLR3 can directly trigger apoptosis in human cancer cells. 2006 J Immunol 176: 4894-4901.

Click on an antigen to find the related products.

  • ● TLR10/CD290

    • DDX0490 - 25F9
      DDX0490 25F9
      TLR10/CD290
      Mouse IgG1
    • DDX0492 - 9F4
      DDX0492 9F4
      TLR10/CD290
      Mouse IgG1
  • ● TLR3/CD283

    • DDX0470 - 619F7.06
      DDX0470 619F7.06
      TLR3/CD283
      Mouse IgM

      IHC for paraffin-embedded tissues, Intracytoplasmic

    • DDX0472 - 722E2.01
      DDX0472 722E2.01
      TLR3/CD283
      Mouse IgM

      Intracytoplasmic

    • DDX0474 - 713E4.06
      DDX0474 713E4.06
      TLR3/CD283
      Mouse IgG1

      IHC for paraffin-embedded tissues, Intracytoplasmic

    • DDX0475 - 716G10.15
      DDX0475 716G10.15
      TLR3/CD283
      Mouse IgM

      IHC for paraffin-embedded tissues, Intracytoplasmic

    • DDX0476 - 1213F10 / TLR3.3
      DDX0476 1213F10 / TLR3.3
      TLR3/CD283
      Mouse IgG1
    • DDX0477 - 1210F1 / TLR3.2
      DDX0477 1210F1 / TLR3.2
      TLR3/CD283
      Mouse IgG1
    • DDX0478 - 1205C5 / TLR3.1
      DDX0478 1205C5 / TLR3.1
      TLR3/CD283
      Mouse IgG1

      IHC for paraffin-embedded tissues

  • ● TLR7/CD287

    • DDX0500 - 66H3
      DDX0500 66H3
      TLR7/CD287
      Mouse IgG1

      IHC for paraffin-embedded tissues

    • DDX0501 - 85D6
      DDX0501 85D6
      TLR7/CD287
      Mouse IgG2a
  • ● TLR8/CD288

    • DDX0480 - 303F1.14
      DDX0480 303F1.14
      TLR8/CD288
      Mouse IgG2a

      Intracytoplasmic, Western-Blot

    • DDX0481 - 307D3.01
      DDX0481 307D3.01
      TLR8/CD288
      Mouse IgG1

      Intracytoplasmic, Western-Blot

    • DDX0482 - 103E11.01
      DDX0482 103E11.01
      TLR8/CD288
      Rat IgG2a

      Intracytoplasmic, Western-Blot

    • DDX0483 - 112H7.15
      DDX0483 112H7.15
      TLR8/CD288
      Rat IgG2a

      Intracytoplasmic, Western-Blot

  • ● IRAK-4

    • DDX0340 - 6F8
      DDX0340 6F8
      IRAK-4
      Mouse IgG1

      IHC for paraffin-embedded tissues

    • DDX0341 - 7D8
      DDX0341 7D8
      IRAK-4
      Mouse IgG1

      IHC for paraffin-embedded tissues

  • ● Myd88

    • DDX1400 - 603E10.05
      DDX1400 603E10.05
      Myd88
      Mouse IgG2b

      IHC for paraffin-embedded tissues

    • DDX1401 - 603E10.06
      DDX1401 603E10.06
      Myd88
      Mouse IgG1