| First Author | Wahlsten JL | Year | 1998 |
| Journal | J Immunol | Volume | 160 |
| Issue | 2 | Pages | 854-9 |
| PubMed ID | 9551921 | Mgi Jnum | J:45179 |
| Mgi Id | MGI:1194518 | Doi | 10.4049/jimmunol.160.2.854 |
| Citation | Wahlsten JL, et al. (1998) Separation of function between the domains of toxic shock syndrome toxin-1. J Immunol 160(2):854-9 |
| abstractText | Toxic shock syndrome toxin-1 (TSST1) is a superantigenic exotoxin produced by certain strains of Staphylococcus aureus Structurally, TSST1 is composed of two domains: residues determined by crystallography to directly interact with MHC II molecules reside within the N-terminal domain, while TSST1 residues critical for superantigenicity are within the C-terminal domain. In this study, we expressed the individual N- and C-terminal domains of TSST1 in Escherichia coli and studied their biologic activities. The TSST1 N-terminal domain (TSST(1-87)) did not induce proliferation of human PBLs or release of TNF-beta, but did induce TNF-alpha release. However, TSST1-elicited proliferation and release of both TNF isoforms were inhibited by a molar excess of TSST(1-87). The TSST1 C-terminal domain (TSST(88-194)) did not bind MHC II molecules, yet it elicited production of TNF-alpha and TNF-beta, and induced TCR Vbeta-specific proliferation similarly to intact TSST1. When covalently cross-linked to tumor cells, TSST(88-194) elicited a local in vivo antitumor response indistinguishable from TSST1. Although intact TSST1 causes lethal shock in vivo, the individual domains of this molecule may have therapeutic potential: the N-terminal domain to antagonize lymphocyte activation and TNF release during acute TSST1-precipitated toxic shock syndrome, and the C-terminal domain to stimulate antitumor responses without MHC II binding. |
