PMID- 9551921
OWN - NLM
STAT- MEDLINE
DCOM- 19980430
LR  - 20061115
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 160
IP  - 2
DP  - 1998 Jan 15
TI  - Separation of function between the domains of toxic shock syndrome toxin-1.
PG  - 854-9
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-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.
FAU - Wahlsten, J L
AU  - Wahlsten JL
AD  - University of Minnesota, Department of Pharmacology, Minneapolis 55455, USA.
FAU - Ramakrishnan, S
AU  - Ramakrishnan S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Bacterial Toxins)
RN  - 0 (Enterotoxins)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Peptide Fragments)
RN  - 0 (Superantigens)
RN  - 0 (enterotoxin F, Staphylococcal)
SB  - IM
MH  - Animals
MH  - *Bacterial Toxins
MH  - Cytotoxicity, Immunologic/drug effects
MH  - Enterotoxins/*chemistry/genetics/metabolism/*physiology
MH  - Female
MH  - Genetic Vectors/immunology
MH  - Histocompatibility Antigens Class II/metabolism
MH  - Humans
MH  - Lymphocyte Activation/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Ovarian Neoplasms/drug therapy/immunology
MH  - Peptide Fragments/metabolism/pharmacology
MH  - Protein Structure, Tertiary
MH  - Staphylococcus aureus/immunology
MH  - Structure-Activity Relationship
MH  - *Superantigens
MH  - Tumor Cells, Cultured
EDAT- 1998/04/29 00:00
MHDA- 1998/04/29 00:01
CRDT- 1998/04/29 00:00
PHST- 1998/04/29 00:00 [pubmed]
PHST- 1998/04/29 00:01 [medline]
PHST- 1998/04/29 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1998 Jan 15;160(2):854-9.