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:
-
- Santa Fe, NM
- Los Alamos, NM
- 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 = {2009},
month = {8}
}
Works referenced in this record:
The Superantigen Streptococcal Pyrogenic Exotoxin C (SPE-C) Exhibits a Novel Mode of Action
journal, August 1997
- Li, Pei-Lin; Tiedemann, Rodger E.; Moffat, S. Louise
- Journal of Experimental Medicine, Vol. 186, Issue 3
Identification and Characterization of Novel Superantigens from Streptococcus pyogenes
journal, January 1999
- Proft, Thomas; Louise Moffatt, S.; Berkahn, Celia J.
- Journal of Experimental Medicine, Vol. 189, Issue 1
Comparative Protein Structure Modeling in Genomics
journal, May 1999
- Sánchez, Roberto; Šali, Andrej
- Journal of Computational Physics, Vol. 151, Issue 1
The Three-dimensional Structure of a Superantigen-like Protein, SET3, from a Pathogenicity Island of the Staphylococcus aureus Genome
journal, June 2002
- Arcus, Vickery L.; Langley, Ries; Proft, Thomas
- Journal of Biological Chemistry, Vol. 277, Issue 35
'Superbug' hurdles key drug barrier
journal, August 2002
- Pearson, Helen
- Nature, Vol. 418, Issue 6897
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
- Matthys, P.; Mitera, T.; Heremans, H.
- Infection and immunity, Vol. 63, Issue 4
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
- Sridhar Prasad, G.; Radhakrishnan, Ramaswamy; Mitchell, David T.
- Protein Science, Vol. 6, Issue 6
Crystal structure of a biologically inactive mutant of toxic shock syndrome toxin-1 at 2.5 A resolution
journal, August 1996
- Papageorgiou, Anastassios C.; Quinn, Conrad P.; Beer, David
- Protein Science, Vol. 5, Issue 8
Role of the T Cell Receptor Ligand Affinity in T Cell Activation by Bacterial Superantigens
journal, June 2001
- Andersen, Peter S.; Geisler, Carsten; Buus, Søren
- Journal of Biological Chemistry, Vol. 276, Issue 36
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
- Papageorgiou, Anastassios C.; Tranter, Howard S.; Acharya, K. Ravi
- Journal of Molecular Biology, Vol. 277, Issue 1
Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library
journal, July 1997
- Atwell, Shane; Ridgway, John B. B.; Wells, James A.
- Journal of Molecular Biology, Vol. 270, Issue 1
Cytokines and related receptor-mediated signaling pathways
journal, October 2002
- Haddad, John J.
- Biochemical and Biophysical Research Communications, Vol. 297, Issue 4
Zinc-mediated Dimerization and Its Effect on Activity and Conformation of Staphylococcal Enterotoxin Type C
journal, April 2002
- Chi, Young-In; Sadler, Ingrid; Jablonski, Lynn M.
- Journal of Biological Chemistry, Vol. 277, Issue 25
Interhelical hydrogen bonds and spatial motifs in membrane proteins: Polar clamps and serine zippers
journal, March 2002
- Adamian, Larisa; Liang, Jie
- Proteins: Structure, Function, and Genetics, Vol. 47, Issue 2
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
- Cottrez, Françoise; Auriault, Claude; Capron, André
- Journal of Immunological Methods, Vol. 172, Issue 1
Staphylococcal enterotoxin genes of classical and new types detected by PCR in France
journal, July 2002
- Rosec, J. P.; Gigaud, O.
- International Journal of Food Microbiology, Vol. 77, Issue 1-2
Intranasal and intramuscular proteosome-staphylococcal enterotoxin B (SEB) toxoid vaccines: immunogenicity and efficacy against lethal SEB intoxication in mice.
journal, January 1996
- Lowell, G. H.; Kaminski, R. W.; Grate, S.
- Infection and immunity, Vol. 64, Issue 5
T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor
journal, January 1992
- Miethke, T.
- Journal of Experimental Medicine, Vol. 175, Issue 1
Costimulatory B7 Molecules in the Pathogenesis of Infectious and Autoimmune Diseases
journal, October 1996
- Reiser, Hans; Stadecker, Miguel J.
- New England Journal of Medicine, Vol. 335, Issue 18
So many ways of getting in the way: diversity in the molecular architecture of superantigen-dependent T-cell signaling complexes
journal, February 2002
- Sundberg, Eric J.; Li, Yili; Mariuzza, Roy A.
- Current Opinion in Immunology, Vol. 14, Issue 1
Superantigens in Human Disease
journal, May 1999
- Bernal, Alejandro; Proft, Thomas; Fraser, John D.
- Journal of Clinical Immunology, Vol. 19, Issue 3, p. 149-157
The Role of Superantigens in Skin Disease.
journal, July 1995
- Leung, Donald Y. M.; Travers, Jeffrey B.; Norris, David A.
- Journal of Investigative Dermatology, Vol. 105, Issue s1
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
- Arcus, Vickery L.; Proft, Thomas; Sigrell, Jill A.
- Journal of Molecular Biology, Vol. 299, Issue 1
Genetic construction, expression, and melanoma-selective cytotoxicity of a diphtheria toxin-related alpha-melanocyte-stimulating hormone fusion protein.
journal, November 1986
- Murphy, J. R.; Bishai, W.; Borowski, M.
- Proceedings of the National Academy of Sciences, Vol. 83, Issue 21
Superantigens – powerful modifiers of the immune system
journal, March 2000
- Fraser, John; Arcus, Vickery; Kong, Philip
- Molecular Medicine Today, Vol. 6, Issue 3
High affinity T cell receptors from yeast display libraries block T cell activation by superantigens11Edited by I. A. Wilson
journal, April 2001
- Kieke, Michele C.; Sundberg, Eric; Shusta, Eric V.
- Journal of Molecular Biology, Vol. 307, Issue 5
Modeling of receptor mimics that inhibit superantigen pathogenesis: MODELING OF RECEPTOR MIMICS
journal, September 2004
- Möllhoff, Margit; Zanden, Hannah B. Vander; Shiflett, Patrick R.
- Journal of Molecular Recognition, Vol. 18, Issue 1
Toxic shock syndrome toxin-1 complexed with a class II major histocompatibility molecule HLA-DR1
journal, December 1994
- Kim, J.; Urban, R.; Strominger, J.
- Science, Vol. 266, Issue 5192
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
- Roussel, Alain; Anderson, Bryan F.; Baker, Heather M.
- Nature Structural Biology, Vol. 4, Issue 8
Structure-Based Design of a Bispecific Receptor Mimic That Inhibits T Cell Responses to a Superantigen
journal, April 2001
- Lehnert, Nancy M.; Allen, David L.; Allen, Beth L.
- Biochemistry, Vol. 40, Issue 14, p. 4222-4228
Interaction of Staphylococcus aureus toxin "superantigens" with human T cells.
journal, November 1989
- Choi, Y. W.; Kotzin, B.; Herron, L.
- Proceedings of the National Academy of Sciences, Vol. 86, Issue 22
Structural basis for the interaction of superantigen with the alternative superantigen-binding receptor p85
journal, February 1997
- Rogers, T.
- Molecular Immunology, Vol. 34, Issue 3
Deletion and fusion analysis of the phage φX174 lysis gene E
journal, January 1985
- Maratea, Denise; Young, Kevin; Young, Ry
- Gene, Vol. 40, Issue 1
‘Knobs-into-holes’ engineering of antibody C H 3 domains for heavy chain heterodimerization
journal, January 1996
- Ridgway, John B. B.; Presta, Leonard G.; Carter, Paul
- "Protein Engineering, Design and Selection", Vol. 9, Issue 7
V beta-specific stimulation of human T cells by staphylococcal toxins
journal, May 1989
- Kappler, J.; Kotzin, B.; Herron, L.
- Science, Vol. 244, Issue 4906
High-affinity binding of staphylococcal enterotoxins A and B to HLA-DR
journal, May 1989
- Fraser, John D.
- Nature, Vol. 339, Issue 6221
Human immunodeficiency virus (HIV) antigens: structure and serology of multivalent human mucin MUC1-HIV V3 chimeric proteins.
journal, January 1995
- Fontenot, J. D.; Gatewood, J. M.; Mariappan, S. V.
- Proceedings of the National Academy of Sciences, Vol. 92, Issue 1
The crystal structure of staphylococcal enterotoxin H: implications for binding properties to MHC class II and TcR molecules
journal, September 2000
- Håkansson, M.; Petersson, K.; Nilsson, H.
- Journal of Molecular Biology, Vol. 302, Issue 3
Evidence for a clonal origin of methicillin resistance in Staphylococcus aureus
journal, January 1993
- Kreiswirth, B.; Kornblum, J.; Arbeit, R.
- Science, Vol. 259, Issue 5092
Galactosamine-induced sensitization to the lethal effects of endotoxin.
journal, November 1979
- Galanos, C.; Freudenberg, M. A.; Reutter, W.
- Proceedings of the National Academy of Sciences, Vol. 76, Issue 11
Design of Chimeric Receptor Mimics with Different TcRVβ Isoforms: TYPE-SPECIFIC INHIBITION OF SUPERANTIGEN PATHOGENESIS
journal, November 2003
- Hong-Geller, Elizabeth; Möllhoff, Margit; Shiflett, Patrick R.
- Journal of Biological Chemistry, Vol. 279, Issue 7
Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen
journal, April 1994
- Jardetzky, Theodore S.; Brown, Jerry H.; Gorga, Joan C.
- Nature, Vol. 368, Issue 6473
Prevention of diseases caused by Staphylococcus aureus using the peptide RIP
journal, September 2000
- Balaban, Naomi; Collins, L. Vincent; Cullor, James S.
- Peptides, Vol. 21, Issue 9