(Wikipedia): Superantigens (SAgs) are a class of antigens result in excessive activation of the immune system. Specifically it causes non-specific activation of T-cells resulting in polyclonal T-cell activation and massive cytokine release. Compared to a normal antigen-induced T-cell response where 0.0001-0.001% of the body’s T-cells are activated, these Superantigens are capable of activating up to 20% of the body’s T-cells. The large number of activated T-cells generates a massive immune response which is not specific to any particular epitope on the supernatigen 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.
- Immune suppression, as induced by its superantigens, might be crucial for SARS-CoV-2 to establish persistent infections.
- Evidence for persistent infection is shown by prolonged viral shedding in feces of several groups of patient
- A persistent virus infection would imply persistent superantigen exposure in the host.
- Superantigens are presented by DCs to T lymphocytes.
- A large subgroup of T lymphocytes is activated, e.g. through their common Vβ Receptor.
- Due to the binding to the outside of the TCR, this binding is independent of the specificity of the TCR.
- A large group of activated T cells have clonal expansion and is capable of (6) immune overreaction, i.e. sepsis.
- Due to the self-destructing nature of sepsis, the immune response is downregulated by negative feedback loops, e.g. by CD4+CD25+ Treg lymphocytes and interleukine-10 (IL-10).
- The result is a partial effective immune response that allows virus persistence.
- The persistent virus infection reactivates the immune system, resulting in an ineffective, but tissue-damaging virus-immune reaction loop.