Journal article
A Single, Engineered Protein Therapeutic Agent Neutralizes Exotoxins from Both Staphylococcus aureus and Streptococcus pyogenes
Clinical and vaccine immunology, Vol.17(11), pp.1781-1789
11/2010
DOI: 10.1128/CVI.00277-10
PMCID: PMC2976085
PMID: 20861327
Abstract
Staphylococcus aureus
and
Streptococcus pyogenes
secrete exotoxins that act as superantigens, proteins that cause hyperimmune reactions by binding the variable domain of the T-cell receptor beta chain (Vβ), leading to stimulation of a large fraction of the T-cell repertoire. To develop potential neutralizing agents, we engineered Vβ mutants with high affinity for the superantigens staphylococcal enterotoxin B (SEB), SEC3, and streptococcal pyrogenic exotoxin A (SpeA). Unexpectedly, the high-affinity Vβ mutants generated against SEB cross-reacted with SpeA to a greater extent than they did with SEC3, despite greater sequence similarity between SEB and SEC3. Likewise, the Vβ mutants generated against SpeA cross-reacted with SEB to a greater extent than with SEC3. The structural basis of the high affinity and cross-reactivity was examined by single-site mutational analyses. The cross-reactivity seems to involve only one or two toxin residues. Soluble forms of the cross-reactive Vβ regions neutralized both SEB and SpeA
in vivo
, suggesting structure-based strategies for generating high-affinity neutralizing agents that can cross-react with multiple exotoxins.
Details
- Title: Subtitle
- A Single, Engineered Protein Therapeutic Agent Neutralizes Exotoxins from Both Staphylococcus aureus and Streptococcus pyogenes
- Creators
- Ningyan Wang - Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455Daiva M Mattis - Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455Eric J Sundberg - Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455Patrick M Schlievert - Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455David M Kranz - Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455
- Resource Type
- Journal article
- Publication Details
- Clinical and vaccine immunology, Vol.17(11), pp.1781-1789
- Publisher
- American Society for Microbiology (ASM)
- DOI
- 10.1128/CVI.00277-10
- PMID
- 20861327
- PMCID
- PMC2976085
- ISSN
- 1556-6811
- eISSN
- 1556-679X
- Language
- English
- Date published
- 11/2010
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984001214002771
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