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Structure-based receptor MIMICS targeted against bacterial superantigen toxins

Patent ·
OSTI ID:968328
 [1];  [2];  [2];  [3]
  1. Santa Fe, NM
  2. Los Alamos, NM
  3. Albuquerque, NM
+ Show Author Affiliations
The invention provides therapeutic compositions useful in the treatment of bacterial superantigen mediated conditions, such as Toxic Shock Syndrome. The compositions comprise genetically engineered bifunctional polypeptides containing a specific T-cell receptor binding domain and a specific MHC class II receptor binding domain, each targeting non-overlapping epitopes on a superantigen molecule against which they are designed. The anti-superantigen "receptor mimetics" or "chimeras" are rationally designed to recreate the modality of superantigen binding directly to both the TCR and the MHC-II receptor, and are capable of acting as decoys for superantigen binding, effectively out-competing the host T-cell and MHC-II receptors, the natural host receptors.
Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM
Sponsoring Organization:
United States Department of Energy
DOE Contract Number:
W-7405-ENG-36
Assignee:
Los Alamos National Security, LLC (Los Alamos, NM)
Patent Number(s):
7,576,183
Application Number:
10/746,959
OSTI ID:
968328
Country of Publication:
United States
Language:
English

References (44)

Intranasal and intramuscular proteosome-staphylococcal enterotoxin B (SEB) toxoid vaccines: immunogenicity and efficacy against lethal SEB intoxication in mice. journal January 1996
High-affinity binding of staphylococcal enterotoxins A and B to HLA-DR journal May 1989
Three-Dimensional Structure of the Complex between a T Cell Receptor β Chain and the Superantigen Staphylococcal Enterotoxin B journal December 1998
The Superantigen Streptococcal Pyrogenic Exotoxin C (SPE-C) Exhibits a Novel Mode of Action journal August 1997
Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library journal July 1997
The crystal structure of staphylococcal enterotoxin H: implications for binding properties to MHC class II and TcR molecules journal September 2000
Galactosamine-induced sensitization to the lethal effects of endotoxin. journal November 1979
Role of the T Cell Receptor Ligand Affinity in T Cell Activation by Bacterial Superantigens journal June 2001
The Three-dimensional Structure of a Superantigen-like Protein, SET3, from a Pathogenicity Island of the Staphylococcus aureus Genome journal June 2002
Identification and Characterization of Novel Superantigens from Streptococcus pyogenes journal January 1999
Design of Chimeric Receptor Mimics with Different TcRVβ Isoforms: TYPE-SPECIFIC INHIBITION OF SUPERANTIGEN PATHOGENESIS journal November 2003
Crystal structure of microbial superantigen staphylococcal enterotoxin B at 1.5 Å resolution: implications for superantigen recognition by MHC class II molecules and T-cell receptors journal March 1998
Structural basis for the interaction of superantigen with the alternative superantigen-binding receptor p85 journal February 1997
Structure-Based Design of a Bispecific Receptor Mimic That Inhibits T Cell Responses to a Superantigen journal April 2001
Deletion and fusion analysis of the phage φX174 lysis gene E journal January 1985
Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D-galactosamine-sensitized and unsensitized mice. journal January 1995
Superantigens – powerful modifiers of the immune system journal March 2000
Cytokines and related receptor-mediated signaling pathways journal October 2002
Human immunodeficiency virus (HIV) antigens: structure and serology of multivalent human mucin MUC1-HIV V3 chimeric proteins. journal January 1995
Toxic shock syndrome toxin-1 complexed with a class II major histocompatibility molecule HLA-DR1 journal December 1994
So many ways of getting in the way: diversity in the molecular architecture of superantigen-dependent T-cell signaling complexes journal February 2002
Modeling of receptor mimics that inhibit superantigen pathogenesis: MODELING OF RECEPTOR MIMICS journal September 2004
V beta-specific stimulation of human T cells by staphylococcal toxins journal May 1989
Prevention of diseases caused by Staphylococcus aureus using the peptide RIP journal September 2000
Evidence for a clonal origin of methicillin resistance in Staphylococcus aureus journal January 1993
Interhelical hydrogen bonds and spatial motifs in membrane proteins: Polar clamps and serine zippers journal March 2002
Zinc-mediated Dimerization and Its Effect on Activity and Conformation of Staphylococcal Enterotoxin Type C journal April 2002
‘Knobs-into-holes’ engineering of antibody C H 3 domains for heavy chain heterodimerization journal January 1996
Analysis of the Vβ specificity of superantigen activation with a rapid and sensitive method using RT PCR and an automatic DNA analyser journal June 1994
Refined structures of three crystal forms of toxic shock syndrome toxin-1 and of a tetramutant with reduced activity: Structures of TSST-1 and of a tetramutant journal June 1997
Genetic construction, expression, and melanoma-selective cytotoxicity of a diphtheria toxin-related alpha-melanocyte-stimulating hormone fusion protein. journal November 1986
Comparative Protein Structure Modeling in Genomics journal May 1999
Costimulatory B7 Molecules in the Pathogenesis of Infectious and Autoimmune Diseases journal October 1996
Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen journal April 1994
The Role of Superantigens in Skin Disease. journal July 1995
High affinity T cell receptors from yeast display libraries block T cell activation by superantigens11Edited by I. A. Wilson journal April 2001
Crystal structure of a biologically inactive mutant of toxic shock syndrome toxin-1 at 2.5 A resolution journal August 1996
Interaction of Staphylococcus aureus toxin "superantigens" with human T cells. journal November 1989
Superantigens in Human Disease journal May 1999
'Superbug' hurdles key drug barrier journal August 2002
T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor journal January 1992
Conservation and variation in superantigen structure and activity highlighted by the three-dimensional structures of two new superantigens from Streptococcus pyogenes 1 1Edited by I. A. Wilson journal May 2000
Staphylococcal enterotoxin genes of classical and new types detected by PCR in France journal July 2002
Crystal structure of the streptococcal superantigen SPE-C: dimerization and zinc binding suggest a novel mode of interaction with MHC class II molecules journal August 1997

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