Superantigens, a Paradox of the Immune Response

Abstract

Staphylococcal enterotoxins are a wide family of bacterial exotoxins with the capacity to activate as much as 20% of the host T cells, which is why they were called superantigens. Superantigens (SAgs) can cause multiple diseases in humans and cattle, ranging from mild to life-threatening infections. Almost all S. aureus isolates encode at least one of these toxins, though there is no complete knowledge about how their production is triggered. One of the main problems with the available evidence for these toxins is that most studies have been conducted with a few superantigens; however, the resulting characteristics are attributed to the whole group. Although these toxins share homology and a two-domain structure organization, the similarity ratio varies from 20 to 89% among different SAgs, implying wide heterogeneity. Furthermore, every attempt to structurally classify these proteins has failed to answer differential biological functionalities. Taking these concerns into account, it might not be appropriate to extrapolate all the information that is currently available to every staphylococcal SAg. Here, we aimed to gather the available information about all staphylococcal SAgs, considering their functions and pathogenicity, their ability to interact with the immune system as well as their capacity to be used as immunotherapeutic agents, resembling the two faces of Dr. Jekyll and Mr. Hyde.

When inflammatory stressors dramatically change, disease phenotypes may transform between autoimmune hematopoietic failure and myeloid neoplasms

“…These microbial components are called superantigens. Superantigen-induced self-reactive antibodies or autoimmune CTLs initiate an immunological attack (superantigen stimulation) ( 133 – 135 ). The same microbes can trigger AIDs in different organ systems through different mechanisms, and AIDs in certain organs can be induced by different microbial infections through different mechanisms.…”

Molecular Characteristics and Pathogenicity of Staphylococcus aureus Exotoxins

“…Three se/sel genes ( sea, sek and seq ) are present together in ϕSa3ms and ϕSa3mw, while a single se/sel gene ( sea or sep ) is carried by ϕMu3A, ϕSa3a, and other prophages [ 30 ]. Two types of plasmids, pIB485 and pF5, carrying se/sel genes have been characterized [ 5 , 9 , 10 , 32 ]. pIB485 is a 27.6 kb plasmid, in which first sed and selj and latter ser were identified.…”

“…These findings underscore the critical role of exotoxins as essential virulence factors closely tied to the establishment and persistence of S. aureus infections. Previous articles have reviewed the function and pathogenicity of superantigen toxins as a paradox of the immune response and their ability to interact with the immune system as well as the capacity to be used as immunotherapeutic agents [ 1 , 9 ]. In this review, we focus on the current understanding of and emerging insights into the molecular characteristics, biological activities, and pathogenicity of S. aureus -produced exotoxins, including superantigen toxins; hemolysins and leukotoxins, which are membrane-damaging toxins; and exfoliative toxins.…”

Current Views about the Inflammatory Damage Triggered by Bacterial Superantigens and Experimental Attempts to Neutralize Superantigen-Mediated Toxic Effects with Natural and Biological Products

“…They are unconventional antigens, which trigger a response by binding outside the complementary determining regions of their target immune receptor macromolecules (antibodies or T cell receptors [ 17 ]. In fact, they activate a large contingent (5–30%) of T cells in comparison to conventional antigens, which stimulate <0.01% of T cells [ 18 ]. Furthermore, superantigens bind outside the peptide-binding groove of MHC class II without internalization and processing and are not MHC class II-restricted.…”