TY - JOUR
T1 - Separation of function between the domains of toxic shock syndrome toxin-1
AU - Wahlsten, Jennifer L.
AU - Ramakrishnan, S.
PY - 1998/1/15
Y1 - 1998/1/15
N2 - 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-β, but did induce TNF-α, 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-α and TNF-β, and induced TCR Vβ-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.
AB - 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-β, but did induce TNF-α, 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-α and TNF-β, and induced TCR Vβ-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.
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M3 - Article
C2 - 9551921
AN - SCOPUS:0031974502
SN - 0022-1767
VL - 160
SP - 854
EP - 859
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -