In:
Clinical and Vaccine Immunology, American Society for Microbiology, Vol. 17, No. 11 ( 2010-11), p. 1781-1789
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.
Type of Medium:
Online Resource
ISSN:
1556-6811
,
1556-679X
DOI:
10.1128/CVI.00277-10
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2010
detail.hit.zdb_id:
1496863-0
