Role of Superantigens in Skin Disease

The skin is an important target for microbial infection. One key strategy by which microbes exacerbate skin disease is via the production of microbial toxins. This chapter focuses on the role of staphylococcal and streptococcal superantigens in human skin diseases, beginning with a review of the properties of superantigens and the mechanisms by which they cause cutaneous immunologic responses. In addition to activated keratinocytes, several other skin cell types constitutively express HLA-DR on their cell surface and are therefore targets for superantigen action. Superantigen-mediated stimulation of monocytes is a consequence of binding and transducing a positive signal through major histocompatibility complex (MHC) class II molecules. The type of antigen-presenting cell (APC) used to present superantigen may influence T-cell development. Staphylococcal superantigens have also been shown to induce human T-cell resistance to corticosteroids and may thereby complicate the treatment of atopic dermatitis (AD) and other inflammatory diseases treated with corticosteroids. The structure of ETB is similar to ETA except that the oxyanion hole, which forms part of the catalytic site, is in the closed or inactive conformation for ETA, but in the open or active conformation for ETB. Both Staphylococcus aureus and Staphylococcus pyogenes are commensal organisms in humans, so the fact that they have the potential to activate the immune response in such a dramatic fashion means that their expression must be tightly controlled and that the immune system must deal with their continuous presence.