Staphylococcal Enterotoxins

Introduction to Staphylococcus aureus

Staphylococcus aureus (S. aureus) is a type of Gram-positive bacterium that belongs to the Firmicutes family, and it is associated with many kinds of infectious diseases and malignant tumors. For instance, bloodstream infections, endocarditis, osteomyelitis, and pneumonia have been considered as common S. aureus infection diseases in humans. Meanwhile, previous studies have demonstrated that people who suffer from chronic diseases, such as diabetes and lung diseases are at greater risk for S. aureus infections. Moreover, more than 110 strains of S. aureus have been isolated and identified from different human tissue types, such as skin. Among them, some strains of S. aureus are capable of producing staphylococcal enterotoxins (SEs) that cause food poisoning and toxic shock syndrome.

Fig.1 Gram staining of Staph aureus showing typical gram-positive cocci. (Soliman, 2014)

Reactivity of γδ T cells to Staphylococcal Enterotoxins

Up to now, there are approximately 20 types of SEs, including SEA, SEB, SEC, and SEI, which have been studied in depth. SEA and SEB have been used as potential superantigens due to their ability to bind with major histocompatibility complex (MHC) class II molecules and interact with T cells to produce specific cytokines. Furthermore, pilot studies have revealed that SEA and SEB can stimulate T cells that express the γδ T cell receptor (TCR) by both antibody-independent and antibody-dependent pathways. Also, recent reports have suggested that γδ T cells can strongly respond to SEs stimulation to trigger immune responses against SE-coated target cells. As a result, SEs have been considered as suitable candidates for the generation of a new class of γδ T cell therapy.

Fig.2 Model of SE interaction with T cell Receptors and class II MHC Molecules. (Balaban, 2000)

SE-Based γδ T Cell Therapy

Currently, γδ T cells have been regarded as an attractive tool for cancer immunotherapy because of their anti-tumor activity and significant role in tumor immunosurveillance. Normally, γδ T cells are unique T cells that consist of a γ chain and a δ chain. γδ T cells can display cytotoxic activity and play an important role in activating innate and adaptive immune responses against various tumor types. Nowadays, researchers have shown that human γδ T cells expressing the Vγ2Vδ2 antigen receptors are essential for γδ TCR recognition of SEA superantigens in disease treatment. Therefore, SEs can be treated as superantigen binding sites for γδ TCR in novel γδ T cell development. For instance, recent studies have indicated that the amino acid residues 20-27 of SEA can be modified for improving the binding capacity of γδ TCR in cancer immunotherapy. Also, these SEs have become a potent γδ TCR target and are involved in killing a wide battery of human tumors from both solid and liquid malignancies.

References

1. Soliman, M. K., et al. Epidemiology and antimicrobial activity of methicillin-resistant Staphylococcus aureus (MRSA) isolated from Nile tilapia (Oreochromis niloticus) during an outbreak in Egypt. Life Science Journal. 2014, 11(10): 1245-1252.
2. Balaban, N., et al. Staphylococcal enterotoxins. International journal of food microbiology. 2000, 61(1): 1-10.