Staphylococcal and streptococcal superantigens: molecular, biological and clinical aspects

Superantigens (SAgs) include a class of certain bacterial and viral proteins exhibiting highly potent lymphocyte-transforming (mitogenic) activity towards human and or other mammalian T lymphocytes. Unlike conventional antigens, SAgs bind to certain regions of major histocompatibility complex (MHC) class II molecules of antigen-presenting cells (APCs) outside the classical antigen-binding groove and concomitantly bind in their native form to T cells at specific motifs of the variable region of the beta chain (Vbeta) of the T cell receptor (TcR). This interaction triggers the activation (proliferation) of the targeted T lymphocytes and leads to the in vivo or in vitro release of high amounts of various cytokines and other effectors by immune cells. Each SAg interacts specifically with a characteristic set of Vbeta motifs. The review summarizes our current knowledge on S. aureus and S. pyogenes superantigen proteins. The repertoire of the staphylococcal and streptococcal SAgs comprises 24 and 8 proteins, respectively. The staphylococcal SAgs include (i) the classical enterotoxins A, B, C (and antigenic variants), D, E, and the recently discovered enterotoxins G to Q, (ii) toxic shock syndrome toxin-1, (iii) exfoliatins A and B. The streptococcal SAgs include the classical pyrogenic exotoxins A and C and the newly identified pyrogenic toxins, G, H, I, J, SMEZ, and SSA. The structural and genomic aspects of these toxins and their molecular relatedness are described as well as the available 3-D crystal structure of some of them and that of certain of their complexes with MHC class II molecules and the TcR, respectively. The pathophysiological properties and clinical disorders related to these SAgs are reviewed.