Superantigens

Abstract

Superantigens (SAgs) are microbial products that have the ability to promote massive activation of immune cells, leading to the release of inflammatory mediators that can ultimately result in hypotension, shock, organ failure and death. They achieve this by simultaneously binding and activating major histocompatibility complex class II molecules on antigen‐presenting cells and T‐cell receptors on T lymphocytes bearing susceptible Vβ regions. Why SAgs function in this manner is still not fully understood although it is thought that the resulting Th1 response may divert the immune system from effective microbial clearance and/or result in the cytokine‐mediated suppression and deletion of activated T cells. Many bacterial and viral species have adapted unrelated SAgs and this article will highlight some of the features of this diverse group of molecules, from the ways in which they interact with the host to the association of various SAgs with acute and chronic diseases.

Key Concepts:

  • Superantigens are toxins produced by many pathogenic bacteria and viruses.

  • Superantigens are defined as molecules that bind to the major histocompatibility complex (MHC) class II and active T cells bearing a particular T‐cell receptor beta chain variable (Vβ) domain.

  • Superantigens are implicated in inducing autoimmunity through the activation of autoreactive T cells that express particular Vβ elements.

  • Superantigens are responsible for staphylococcal and streptococcal toxic shock.

  • The superantigens of Staphylococcus aureus are responsible for staphylococcal food poisoning.

  • The endogenous superantigen of the mouse mammary tumour virus (MMTV) causes deletion of T cells bearing a particular Vβ element, amplification of infected B cells and transmission of virus to the offspring.

Keywords: viruses; bacteria; lymphocytes; immunology; MHC; TCR; autoimmunity; toxic shock

Figure 1.

Superantigen presentation. In the centre panel conventional peptide antigens (shown in red) bind to the groove of the major histocompatibility complex (MHC) class II molecules on the surface of antigen‐presenting cells and interact with the hypervariable segments of both the α and β chains of the T‐cell receptor (TCR). Superantigens (shown in orange) associate with MHC class II outside the peptide‐binding groove and concurrently bind the variable region on β chains of susceptible TCR. The left panel shows the possible binding of an endogenously expressed MMTVSAg (which may or may not be extracellularly cleaved) whereas the right side panel shows the interaction of an exogenous SAg with MHC II and the TCR.

Figure 2.

Superantigen structures. (a) The structure of TSST‐1, a representative of the staphylococcal/streptococcal SAg family. The β‐grasp domain (left) is separated from the OB‐fold domain (right) by the central alpha helix (blue). The prosite motifs PS00278 (blue) and PS00277 (red) are highlighted. (b) The structure of YPMa. (c) The structure of MAM as it was determined when bound to MHC II (top) or in its apo form (bottom) as a domain‐swapped dimer.

Figure 3.

Representative response of Vβ8+ T cells to the bacterial superantigen staphylococcal enterotoxin B (SEB) in the popliteal lymph nodes. The different phases of the response are depicted by regions (I) amplification; (II) deletion; and (III) anergy.

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Further Reading

Kotb M and Fraser JD (eds) (2007) Superantigens: Molecular Basis and Role in Human Disease. ISBN 978‐1‐55581‐3. Washington, DC: ASM Press.

Krakauer T (ed.) (2002) Superantigen Protocols (Methods in Molecular Biology). ISBN: 0896039846. Totowa, NJ: Humana Press.

Marone G (ed.) (2007) Superantigens and Superallergens. ISBN 978–3–8055–8266–7. Basel: Karger.

Stow NW, Douglas R, Tantilipikorn P and Lacroix JS (2010) Superantigens. Otolaryngologic Clinics of North America 43(3): 489–502, vii.

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Langley, Ries J, and Renno, Toufic(Nov 2011) Superantigens. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001216.pub2]