The superantigenic activity of streptococcal pyrogenic exotoxin B is independent of the protease activity

The nature of the mitogenic activity of pyrogenic streptococcal exotoxin B, also known as streptococcal cysteine protease, has been debated in the lit erature. streptococcal exotoxin B has been shown to cleave interleukin-1 be ta precursor and create biologically active interleukin-1 beta, a major cyt okine mediating inflammation and shock. This activity could mimic the mitog enicity and cytokine release induced by superantigens in lymphocyte stimula ting experiments. In this study, the protease activity of streptococcal exo toxin B was irreversibly inhibited by covalent binding of a tripeptide and the superantigenic properties of streptococcal exotoxin B were found not to be influenced by this inactivation. Native as well as protease-inactivated streptococcal exotoxin B was shown to stimulate T-cell proliferation witho ut a need of metabolically active antigen presenting cells. Furthermore, st reptococcal exotoxin B-induced T-cell proliferation was shown to require HL A-DQ since addition of HLA-DQ monoclonal antibodies totally inhibited the m itogenic activity of streptococcal exotoxin B, indicating that streptococca l exotoxin B, as other superantigens, makes direct contact with the T-cell receptor via HLA class II. The aim of this study was to characterize the re lationship between the proteolytic and superantigenic properties of strepto coccal exotoxin B. (C) 1999 Federation of European Microbiological Societie s. Published by Elsevier Science B.V. All rights reserved.