By: Suzanne Canada, Ph.D.
Tanager Medical Writing
The world of microbial pathology is often understood as a system of various organisms who are trying to survive by using plants or animals as “hosts”. The dynamics of these systems can described the pathogen as trying to establish a living space for itself, while the “host” does its best to evict these unwelcome tenants. One of the most commonly known pathogens is Staphylococcus, a highly adaptable and ubiquitous opportunistic pathogen. The staphylococcal enterotoxins are small heat-stable proteins used by Staphylococcus strains to help them in their attempt to colonize.
One of the most notable and yet poorly understood properties of Staphylococcal enterotoxin B (SEB) is its potent ability to stimulate immune T-cell proliferation. It doesn’t make sense that a bacterium that is intent on colonization would find it advantageous to promote an immune response. On the other hand, it could have been coincidence or selective adaptation that the mammalian immune system learned to recognize one of its most ubiquitous enemies. After many of years of observation by immunologists that lymphocytes proliferated when enterotoxin was added to whole blood in test tubes, John Kappler dubbed them superantigens (Kappler, 1989).
The following references use SEB as a control for stimulate T-cells:
- Nakanjako D., Ssewanyana I., Nabatanzi R., Kiragga A., Kamya M., Cao H., Mayanja-Kizza H., (2013) Impaired T-cell proliferation among HAART-treated adults with suboptimal CD4 recovery in an African cohort. BMC Immunol. 14: 26. PMID: 23786370
- Scheible K., Secor-Socha S., Wightman T., Wang H., Mariani TJ., Topham DJ., Pryhuber G., Quataert S., (2012) Stability of T cell phenotype and functional assays following heparinizedumbilical cord blood collection. Cytometry A. 81(11):937-49. PMID: 23027690
- Stam J., Abdulahad W., Huitema MG., Roozendaal C., Limburg PC., van Stuijvenberg M,. Schölvinck EH., (2011) Fluorescent cell barcoding as a tool to assess the age-related development of intracellular cytokine production in small amounts of blood from infants. PLoS One 6(10):e25690. PMID: 22043291
- Xu Y., Fernandez C., Alcantara S., Bailey M., De Rose R., Kelleher AD., Zaunders J., Kent SJ., (2013) Serial study of lymph node cell subsets using fine needle aspiration in pigtail macaques. J Immunol Methods 394(1-2):73-83. PMID: 23702165
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The significance of T-cell stimulation by SEB has been the topic of much hypothesis and discussion. The site of SEB binding to T-cells has been investigated to a molecular level (Li, 1998; Saline, 2010). SEB and other enterotoxins are used in investigations of innate immunity to bacterial infections, signaling by toll-like receptors, and the modulation of inflammatory responses, especially cytokine stimulation (Kumar, 2010; Ortega, 2010; Vidlak, 2011; Edwards, 2012). The function, origin, and role in adaptation that t-cell stimulation serves will be a topic of ongoing scientific debate. In any case it is clear that SEB and other bacterial superantigens are very good at bypassing the antigen recognition by T-cells (Sundberg, 2002; Kumar, 2013). Some investigation into the biochemical level of SEB recognition by T-cells has indicated that this protein shares antigenic sequences with known self-antigens in mammals (White, 1989). This observation supports the theory that activation of T-cells plays a role in noninfectious diseases like autoimmune responses (Edwards, 1996; Kumar, 1997; Li, 1996; Sundberg, 2002), which might make SEB an appropriate stimulator when studying these mechanisms of disease. List Labs provides for SEB produced in a native Staphylococcus aureus, for research purposes that provides potent stimulation of the immune system and cytokine production.
- Edwards CK., Zhou T., Zhang J., Baker TJ., De M., Long RE., Borcherding DR., Bowlin TL., Bluethmann H., Mountz JD., (1996) Inhibition of superantigen-induced proinflammatory cytokine production and inflammatory arthritis in MRL-lpr/lpr mice by a transcriptional inhibitor of TNF-alpha. J Immunol 157(4): 1758-1772. PMID: 8759766
- Edwards LA., O’Neill C., Furman MA., Hicks S., Torrente F., Pérez-Machado M., Wellington EM., Phillips AD., Murch SH., (2012) Enterotoxin-producing staphylococci cause intestinal inflammation by a combination of direct epithelial cytopathy and superantigen-mediated T-cell activation. Inflamm Bowel Dis 18(4): 624-640. PMID: 21887731
- Kappler J., Kotzin B., Herron L., Gelfand EW., Bigler RD., Boylston A., Carrel S., Posnett DN., Choi Y., Marrack P., (1989) V beta-specific stimulation of human T cells by staphylococcal toxins. Science 244(4906): 811-813. PMID: 2524876
- Kumar S., Colpitts SL., Ménoret A., Budelsky AL., Lefrancois L., Vella AT., (2013) Rapid alphabeta T-cell responses orchestrate innate immunity in response to Staphylococcal enterotoxin A. Mucosal Immunol 6(5): 1006-1015. PMID: 23321986
- Kumar S., Ménoret A., Ngoi SM., Vella AT., (2010) The systemic and pulmonary immune response to staphylococcal enterotoxins. Toxins (Basel) 2(7): 1898-1912. PMID: 22069664
- Kumar V., Aziz F., Sercarz E., Miller A ., (1997) Regulatory T cells specific for the same framework 3 region of the Vbeta8.2 chain are involved in the control of collagen II-induced arthritis and experimental autoimmune encephalomyelitis. J Exp Med 185(10): 1725-1733. PMID: 9151697
- Li H., Llera A., Tsuchiya D., Leder L., Ysern X., Schlievert PM., Karjalainen K., Mariuzza RA., (1998) Three-dimensional structure of the complex between a T cell receptor beta chain and the superantigen staphylococcal enterotoxin B. Immunity 9(6): 807-816. PMID: 9881971