Antigen which strongly activates the immune system
SEB, a typical bacterial superantigen (PDB:3SEB). The β-grasp domain is shown in red, the β-barrel in green, the "disulfide loop" in yellow.SEC3 (yellow) complexed with an MHC class II molecule (green & cyan). The SAgs binds adjacent to the antigen presentation cleft (purple) in the MHC-II.Schematic representation of MHC class II.The T-cell receptor complex with TCR-α and TCR-β chains, CD3 and ζ-chain accessory molecules.
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.[1] SAgs are produced by some pathogenic viruses and bacteria most likely as a defense mechanism against the immune system.[2] 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.[3] Furthermore, Anti-CD3 and Anti-CD28 antibodies (CD28-SuperMAB) have also shown to be highly potent superantigens (and can activate up to 100% of T cells).
The large number of activated T-cells generates a massive immune response which is not specific to any particular epitope on the SAg thus undermining one of the fundamental strengths of the adaptive immune system, that is, its ability to target antigens with high specificity. More importantly, the large number of activated T-cells secrete large amounts of cytokines, the most important of which is Interferon gamma. This excess amount of IFN-gamma in turn activates the macrophages. The activated macrophages, in turn, over-produce proinflammatory cytokines such as IL-1, IL-6 and TNF-alpha. TNF-alpha is particularly important as a part of the body's inflammatory response. In normal circumstances it is released locally in low levels and helps the immune system defeat pathogens. However, when it is systemically released in the blood and in high levels (due to mass T-cell activation resulting from the SAg binding), it can cause severe and life-threatening symptoms, including septic shock and multiple organ failure.
^Levinson, Warren (2020). Review of Medical Microbiology and Immunology (16th ed.). USA: McGraw-Hill Education. p. 530. ISBN 9781260116717.
^Li H., Llera A., Malchiodi E.L., Mariuzza R.A. The structural basis of T cell activation by superantigens. Annu. Rev. Immunol. 1999;17:435–466. doi: 10.1146/annurev.immunol.17.1.435.
Superantigens (SAgs) are a class of antigens that result in excessive activation of the immune system. Specifically they cause non-specific activation...
at 100 °C for a few minutes. Gastroenteritis occurs because SEB is a superantigen, causing the immune system to release a large amount of cytokines that...
"Crystal structure of microbial superantigen staphylococcal enterotoxin B at 1.5 A resolution: implications for superantigen recognition by MHC class II molecules...
of the bacterial species Streptococcus pyogenes. SpeA and speC are superantigens, which induce inflammation by nonspecifically activating T cells and...
colonization of its host, this bacterium possesses many virulence factors. Superantigens, bacterial adhesions, and the actions of Yops (which are bacterial proteins...
disease most commonly caused by infection of superantigen-producing Staphylococcus aureus. The superantigen toxin secreted in S. aureus infections is TSS...
the S. pyogenes superantigen speG, has been documented in some S. dysgalactiae strains. However, it only appears to possess superantigen-capabilities in...
syndrome (TSLS). The underlying mechanism involves the production of superantigens during an invasive streptococcus infection or a localized staphylococcus...
enterotoxin Pertussis toxin Pseudomonas exotoxin Extracellular adenylate cyclase Mechanisms type I Superantigen type II Pore-forming toxin type III AB toxin/AB5...
these toxins are associated with specific diseases. Superantigens Antigens known as superantigens can induce toxic shock syndrome (TSS). This group comprises...
Two examples are described below. Superantigens are produced by several bacteria. The best-characterized superantigens are those produced by the strains...
exposure via ingestion, inhalation, injection, or contact with skin. Superantigen – A class of antigens that cause non-specific activation of T-cells,...
IgM antibody: structural basis for recognition of B-cell receptors and superantigen activity". Proceedings of the National Academy of Sciences of the United...
the antigen-binding fragment (Fab) of a monoclonal antibody with the superantigen staphylococcal enterotoxin A (SEA/E-120, "estafenatox"). The Fab binds...
enterotoxin Pertussis toxin Pseudomonas exotoxin Extracellular adenylate cyclase Mechanisms type I Superantigen type II Pore-forming toxin type III AB toxin/AB5...
cell expressing GFP-actin (green) and Raji B cell stained with CMAC (blue). Synapse formation was induced by Staphylococcal enterotoxin E superantigen....
MMTV codes for the retroviral structural genes and additionally for a superantigen. This stimulates T lymphocytes with a certain type of V beta chain in...
shock syndrome. Streptococcus species produce M protein, which acts as a superantigen, stimulating a massive systemic immune response which is not effective...
but uncommon for molecular mimicry to lead to an autoimmune disease. Superantigens are composed of viral or bacterial proteins and can hijack the clonal...
There has been debate as to whether the infectious agent might be a superantigen (i.e. one commonly associated with excessive immune system activation)...
(Env), regulator of MMTV expression (Rem) and superantigen (Sag) proteins found in MMTV. The viral superantigen is the most variable region within the betaretrovirus...
post-streptococcal glomerulonephritis. These toxins are also known as "superantigens" because they can cause an extensive immune response by activating some...
enterotoxin Pertussis toxin Pseudomonas exotoxin Extracellular adenylate cyclase Mechanisms type I Superantigen type II Pore-forming toxin type III AB toxin/AB5...
enterotoxin Pertussis toxin Pseudomonas exotoxin Extracellular adenylate cyclase Mechanisms type I Superantigen type II Pore-forming toxin type III AB toxin/AB5...
enterotoxin Pertussis toxin Pseudomonas exotoxin Extracellular adenylate cyclase Mechanisms type I Superantigen type II Pore-forming toxin type III AB toxin/AB5...
Lewis, P.; Howarth, P. (2011-04-01). "Staphylococci and staphylococcal superantigens in asthma and rhinitis: a systematic review and meta-analysis". Allergy...
enterotoxin Pertussis toxin Pseudomonas exotoxin Extracellular adenylate cyclase Mechanisms type I Superantigen type II Pore-forming toxin type III AB toxin/AB5...
enterotoxin Pertussis toxin Pseudomonas exotoxin Extracellular adenylate cyclase Mechanisms type I Superantigen type II Pore-forming toxin type III AB toxin/AB5...
Global Information
