Superantigen (SAg): Examples and Roles

Superantigens are microbial peptides that can polyclonally activate a large fraction of T cells (up to 20%). They escape normal antigen processing by antigen presenting cells (APCs) and can directly bind to T cell receptor (TCR).

This binding of TCR with MHC-II by superantigen results into polyclonal activation of T cells which can ultimately result in life-threatening autoimmune responses, even deaths.

Superantigen interaction with TCR-MHC-II (Source)

Superantigens bind simultaneously to the domain of a T-cell receptor and to the α chain of a class II MHC molecule. Crosslinkage of a T-cell receptor and class II MHC molecule produces an activating signal that induces T-cell activation and proliferation. The number of T cells sharing Vβ domain is high as a consequence superantigen activates large number of T Cells with different specificity.

Superantigens polyclonally activate a large fraction (up to 25%) of the T cells, setting off massive immune response whereas in T dependent antigen only a fraction of (1 in 10^6 -10^4) of the T cell population is able to recognize the antigen and become activated. The massive activation of T cells results in overproduction of TH cell cytokines (TNF alpha, IL-1, IL-6) leading to systemic toxicity, multi-organ failure and even death in some cases.

Both exogenous and endogenous superantigens have been identified. Exogenous superantigens are soluble proteins secreted by bacteria e.g. Staphylococcus aureus (TSST-1) and Streptococcus pyogenes (exotoxin A and B) . Endogenous superantigens are cell-membrane proteins are encoded by certain viruses that infect mammalian cells e.g. mouse mammary tumour virus (MMTV) and Epstein-Barr virus (EBV) that infect mammalian cells.

Examples of Bacterial Superantigens and their roles:

  1. Staphylococcal enterotoxins: Food poisoning
  2. Staphylococcal toxic shock toxin (TSST-1): Toxic shock syndrome
  3. Staphylococcal exfoliating toxins: Scalded skin syndrome
  4. Streptococcal pyrogenic exotoxins (exotoxin A and exotoxin B): Shock

Conventional antigen Vs. Superantigen

Some of  the key features of conventional antigen and superantigen is summarized in the table below:

Properties Conventional Antigen Superantigen
Nature Antigens are foreign substances (mostly proteins, polysaccharide) or altered self proteins that induces specific immune response. Superantigens are microbial peptides that can polyclonally activate large portion of T cells.
Antigen Processing and Presentation Conventional protein antigens are processed by B cell and a peptide of the protein antigen is presented to its matching antigen-specific CD4 T cell via MHC-II-peptide:TCR Superantigens are not processed intracellularly, instead, they bind class II MHC molecules as intact macromolecules and bind outside of the peptide-antigen binding groove.
  Binding with T cells Classical antigens bind to the highly variable peptide groove of the T-cell receptor.   Superantigen binds/interact with the more conserved Vβ region of T cell receptor. All T cells that express that particular Vβ region are subject to activation regardless of antigen specificity.
Need of costimulatory signal Successful T cell activation by conventional antigen requires multiple signals. Presentation of MHC-II-peptide-TCR is not enough to stimulate T cells. It requires co-stimulatory signal provided by an interaction between members of the B7 family (either CD80 or CD86) on APCs and CD28 on T cells. Superantigens can activate T lymphocytes in the absence of costimulatory molecules.
T Cell Activation Conventional peptide antigens generally activate only the small fraction of the T cell population (i.e. <0.01% T Cells). Superantigens (SAgs) have the ability to stimulate 2-30% of the T cell repertoire.

References and further reading

About tankeshwar 385 Articles
Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion, I am working as an Asst. Professor and Microbiologist at Department of Microbiology and Immunology, Patan Academy of Health Sciences, Nepal. If you want me to write about any posts that you found confusing/difficult, please mention in the comments below.

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