Superantigens include bacterial products (mainly ofstreptococci and staphylococci) that stimulate T cells to proliferate nonspecifically through interaction with class II major histocompatibility complex products on antigen-presenting cells and then with variable regions on the fJ chain of the T cell receptor complex. They include pyrogenic toxins (streptococcal scarlet fever toxins of serotypes A, B, and C, toxic shock syndrome toxin 1, and staphylococcal enterotoxin serotypes A, B, Cn , D, E, and G), streptococcal M protein, staphylococcal exfoliative toxin, and recently identified pyrogenic toxins made by groups B, C, F, and G streptococci and Streptococcus sanguis. Pyrogenic toxin superantigens cause acute toxic shock syndrome and are associated with toxic shock-like syndromes. Superantigens cause symptoms via release of immune cytokines. These proteins should be considered potential causes of illnesses such as rheumatic fever, arthritis, Kawasaki syndrome, atopic dermatitis, and guttate psoriasis because of their potent immune system-altering capacity.
In recent years there has been an explosion ofinformation concerning microbial superantigens and their possible roles in both acute and chronic diseases in humans. Thus far, superantigens are restricted to the bacterial and viral pathogens listed in table I. Perhaps the most well characterized is the large family of pyrogenic toxins made by Staphylococcus aureus and group A streptococci, including staphylococcal toxic shock syndrome (TSS) toxin I (TSST-I) and the enterotoxins, designated serotypes A, B, Cn, D, E, and G, and the group A streptococcal pyrogenic exotoxins (SPEs, scarlet fever toxins) serotypes A-C. All of these toxins share the ability to induce high fever, enhance host susceptibility to lethal endotoxin shock, and induce T cell proliferation without regard to the antigenic specificity ofthe T cell (superantigenicity). The effects of these activities on the host result in significant multisystem illnesses. First, it is important to be able to distinguish between superantigenic activity and typical T cell recognition ofan antigen. As shown in figure IA, the typical protein antigen is initially taken up by an antigenpresenting cell (APC), such as a macrophage, B cell, or dendritic cell, where the antigen is processed into antigenic peptides by proteases. The antigenic peptides bind in a groove formed by interaction of the a and fJ chains of the class II major histocompatibility complex (MHC), and the peptideMHC complex becomes expressed on the surface of the APC. The T cell then interacts with that complex on the APC surface through the antigen-specific T cell receptor (TCR), releasing cytokines and “helping” all specific immune responses, whether T or B cell mediated. Unlike antigens, superantigens do not require processing by APCs but interact directly with relatively invariant regions of the class II MHC molecules and outside of the groove area (figure IB). In this way superantigens can interact with a variety ofclass II MHC molecules. The superantigen- MHC complex interacts with the TCR such that the superantigen reacts with the T cell outside the groove area for recognition of antigenic peptides. Thus, the interaction of superantigens with T cells is nonspecific. There is some specificity involved, however, since the superantigen interacts with the variable (V) part of the fJ chain of the TCR. Thus, all T cells bearing a recognized VfJ will be stimulated by the superantigen, without regard for the antigenic specificity of the T cell. Each superantigen will recognize one to five VfJs, and each superantigen has its own signature VfJprofile. The result of such T cell stimulation by superantigens is massive Iymphokine and monokine release.