*Review* **Superantigens, a Paradox of the Immune Response**

**Sofia Noli Truant, Daniela María Redolfi, María Belén Sarratea, Emilio Luis Malchiodi and Marisa Mariel Fernández \***

> Cátedra de Inmunología—IDEHU (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 4 Piso, Ciudad Autónoma de Buenos Aires 1113, Argentina **\*** Correspondence: mmfernan@ffyb.uba.ar; Tel.: +54-11-52874411

> **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.

> **Keywords:** staphylococcal superantigen; enterotoxin; toxin pathogenicity; immunomodulation; molecular and cellular targets

> **Key Contribution:** Bacterial superantigens manipulate the host immune response favoring the spread and colonization of *Staphylococcus aureus*, causing multiple affections. This review summarizes the current knowledge on every superantigen described, focusing on the dual nature of these toxins.
