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Title: Structure-based receptor MIMICS targeted against bacterial superantigen toxins

Abstract

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.

Inventors:
 [1];  [2];  [2];  [3]
  1. Santa Fe, NM
  2. Los Alamos, NM
  3. Albuquerque, NM
Issue Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
968328
Patent Number(s):
7576183
Application Number:
10/746,959
Assignee:
Los Alamos National Security, LLC (Los Alamos, NM)
Patent Classifications (CPCs):
A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07K - PEPTIDES
DOE Contract Number:  
W-7405-ENG-36
Resource Type:
Patent
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Gupta, Goutam, Hong-Geller, Elizabeth, Shiflett, Patrick R, and Lehnert, Nancy M. Structure-based receptor MIMICS targeted against bacterial superantigen toxins. United States: N. p., 2009. Web.
Gupta, Goutam, Hong-Geller, Elizabeth, Shiflett, Patrick R, & Lehnert, Nancy M. Structure-based receptor MIMICS targeted against bacterial superantigen toxins. United States.
Gupta, Goutam, Hong-Geller, Elizabeth, Shiflett, Patrick R, and Lehnert, Nancy M. Tue . "Structure-based receptor MIMICS targeted against bacterial superantigen toxins". United States. https://www.osti.gov/servlets/purl/968328.
@article{osti_968328,
title = {Structure-based receptor MIMICS targeted against bacterial superantigen toxins},
author = {Gupta, Goutam and Hong-Geller, Elizabeth and Shiflett, Patrick R and Lehnert, Nancy M},
abstractNote = {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.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Aug 18 00:00:00 EDT 2009},
month = {Tue Aug 18 00:00:00 EDT 2009}
}

Works referenced in this record:

The Superantigen Streptococcal Pyrogenic Exotoxin C (SPE-C) Exhibits a Novel Mode of Action
journal, August 1997


Identification and Characterization of Novel Superantigens from Streptococcus pyogenes
journal, January 1999


Comparative Protein Structure Modeling in Genomics
journal, May 1999


The Three-dimensional Structure of a Superantigen-like Protein, SET3, from a Pathogenicity Island of the Staphylococcus aureus Genome
journal, June 2002


'Superbug' hurdles key drug barrier
journal, August 2002


Crystal structure of a biologically inactive mutant of toxic shock syndrome toxin-1 at 2.5 A resolution
journal, August 1996


Role of the T Cell Receptor Ligand Affinity in T Cell Activation by Bacterial Superantigens
journal, June 2001


Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library
journal, July 1997


Cytokines and related receptor-mediated signaling pathways
journal, October 2002


Zinc-mediated Dimerization and Its Effect on Activity and Conformation of Staphylococcal Enterotoxin Type C
journal, April 2002


Interhelical hydrogen bonds and spatial motifs in membrane proteins: Polar clamps and serine zippers
journal, March 2002


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


Staphylococcal enterotoxin genes of classical and new types detected by PCR in France
journal, July 2002


Costimulatory B7 Molecules in the Pathogenesis of Infectious and Autoimmune Diseases
journal, October 1996


So many ways of getting in the way: diversity in the molecular architecture of superantigen-dependent T-cell signaling complexes
journal, February 2002


Superantigens in Human Disease
journal, May 1999


The Role of Superantigens in Skin Disease.
journal, July 1995


Genetic construction, expression, and melanoma-selective cytotoxicity of a diphtheria toxin-related alpha-melanocyte-stimulating hormone fusion protein.
journal, November 1986


Superantigens – powerful modifiers of the immune system
journal, March 2000


High affinity T cell receptors from yeast display libraries block T cell activation by superantigens11Edited by I. A. Wilson
journal, April 2001


Modeling of receptor mimics that inhibit superantigen pathogenesis: MODELING OF RECEPTOR MIMICS
journal, September 2004


Toxic shock syndrome toxin-1 complexed with a class II major histocompatibility molecule HLA-DR1
journal, December 1994


Structure-Based Design of a Bispecific Receptor Mimic That Inhibits T Cell Responses to a Superantigen
journal, April 2001


Interaction of Staphylococcus aureus toxin "superantigens" with human T cells.
journal, November 1989


Deletion and fusion analysis of the phage φX174 lysis gene E
journal, January 1985


‘Knobs-into-holes’ engineering of antibody C H 3 domains for heavy chain heterodimerization
journal, January 1996


V beta-specific stimulation of human T cells by staphylococcal toxins
journal, May 1989


Human immunodeficiency virus (HIV) antigens: structure and serology of multivalent human mucin MUC1-HIV V3 chimeric proteins.
journal, January 1995


The crystal structure of staphylococcal enterotoxin H: implications for binding properties to MHC class II and TcR molecules
journal, September 2000


Evidence for a clonal origin of methicillin resistance in Staphylococcus aureus
journal, January 1993


Galactosamine-induced sensitization to the lethal effects of endotoxin.
journal, November 1979


Design of Chimeric Receptor Mimics with Different TcRVβ Isoforms: TYPE-SPECIFIC INHIBITION OF SUPERANTIGEN PATHOGENESIS
journal, November 2003


Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen
journal, April 1994


Prevention of diseases caused by Staphylococcus aureus using the peptide RIP
journal, September 2000