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 in polyclonal activation of T cells, ultimately resulting in life-threatening autoimmune responses, even deaths.
Superantigen interaction with TCR-MHC-II (Source)
Superantigens bind simultaneously to the Vβ domain of a T-cell receptor and the α chain of a class II MHC molecule. Cross linkage 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 many T Cells with different specificity.
Superantigens polyclonally activate a large fraction (up to 25%) of the T cells, producing a massive immune response. In contrast, in T-dependent antigen, only a fraction of (1 in 10^6 -10^4) of the T cell population can 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.
Both exogenous and endogenous superantigens have been identified. Exogenous superantigens are soluble proteins secreted by bacteria e.g. Staphylococcus aureus (TSST-1) and Streptococcus
Examples of Bacterial Superantigens and their roles:
- Staphylococcal enterotoxins: Food poisoning
- Staphylococcal toxic shock toxin (TSST-1): Toxic shock syndrome
- Staphylococcal exfoliating toxins: Scalded skin syndrome
- 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:
Difference between conventional antigen and superantigen
| Properties | Conventional Antigen | Superantigen |
| Nature | Antigens are foreign substances (primarily proteins and polysaccharide) or altered self-proteins that induces a specific immune response. | Superantigens are microbial peptides that can polyclonally activate a 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 | 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 a small fraction of the T cell population (i.e., <0.01% of T Cells). | Superantigens (SAgs) can stimulate 2-30% of the T cell repertoire. |
References and further reading
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Thanks very much for this straightforward explanation of Superantigens! Much easier to explain to my own students!