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Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have reached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13. Humans lack genes for TLR11, TLR12 and TLR13 and mice lack a functional gene for TLR10. The receptors TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the cell membrane, whereas TLR3, TLR7, TLR8, and TLR9 are located in intracellular vesicles.
Superantigens (SAgs) are a class of antigens that result in excessive activation of the immune system. Specifically they cause non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release. Superantigens act by binding to the MHC proteins on antigen-presenting cells (APCs) and to the TCRs on their adjacent helper T-cells, bringing the signaling molecules together, and thus leading to the activation of the T-cells, regardless of the peptide displayed on the MHC molecule. SAgs are produced by some pathogenic viruses and bacteria most likely as a defense mechanism against the immune system. Compared to a normal antigen-induced T-cell response where 0.0001-0.001% of the body's T-cells are activated, these SAgs are capable of activating up to 20% of the body's T-cells. Furthermore, Anti-CD3 and Anti-CD28 antibodies (CD28-SuperMAB) have also shown to be highly potent superantigens.
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References
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- 1 2 "Akademie Personen" (PDF), Akademie Aktuell (in German), vol. 21, Bavarian Academy of Sciences, p. 61, February 2007, archived from the original (PDF) on 22 July 2011, retrieved 14 May 2011
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- ↑ Wagner, H.; Röllinghoff, M. (1 December 1978). "T-T-cell interactions during the vitro cytotoxic allograft responses. I. Soluble products from activated Lyl+ T cells trigger autonomously antigen-primed Ly23+ T cells to cell proliferation and cytolytic activity". Journal of Experimental Medicine . 148 (6): 1523–1538. doi:10.1084/jem.148.6.1523. PMC 2185095 . PMID 309919.
- ↑ Miethke, T.; Wahl, C.; Heeg, K.; Echtenacher, B.; Krammer, P.H.; Wagner, H. (1 January 1992). "T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor". Journal of Experimental Medicine . 175 (1): 91–98. doi:10.1084/jem.175.1.91. PMC 2119077 . PMID 1730929.
- 1 2 Schütz, Martin (6 March 2007). "Neue Mitglieder in die Bayerische Akademie der Wissenschaften gewählt" [New members elected to the Bavarian Academy of Sciences] (Press release) (in German). Bayerische Akademie der Wissenschaften . Retrieved 15 May 2011.
- ↑ F., Heil; Hemmi, H.; Hochrein, H.; Ampenberger, F.; Kirschning, C.; Akira, S.; Lipford, G.; Wagner, H.; Bauer, S. (5 March 2004). "Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8". Science. 303 (5663): 1526–1529. Bibcode:2004Sci...303.1526H. doi: 10.1126/science.1093620 . PMID 14976262. S2CID 1680581.
- ↑ Oldenburg, M.; Krüger, A.; Ferst, R.; Kaufmann, A.; Nees, G.; Sigmund, A.; Bathke, B.; Lauterbach, H.; Suter, M.; Dreher, S.; Koedel, U.; Akira, S.; Kawai, T.; Buer, J.; Wagner, H.; Bauer, S.; Hochrein, H.; Kirschning, C.J. (31 August 2012). "TLR13 recognizes bacterial 23S rRNA devoid of erythromycin resistance-forming modification". Science. 337 (6098): 1111–1115. Bibcode:2012Sci...337.1111O. doi:10.1126/science.1220363. PMID 22821982. S2CID 206540638.
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