Engineering Soluble, High Affinity Receptor Antagonists for Bacterial Exotoxins

Chapter four describes the engineering of murine Vbeta8.2 for picomolar affinity to staphylococcal enterotoxin B (SEB). As the known contact regions had already been heavily mutagenized, additional engineering of the Vbeta was performed through extension of the CDR1 loop. Soluble forms of the high-affinity Vbeta regions were tested for their ability to inhibit SEB-mediated T cell cytotoxicity in vitro. As the affinity of the Vbeta regions increased, the amount of protein needed to neutralize 50% of the toxin activity correspondingly decreased. These Vbeta regions were also tested in various rabbit models of toxic shock by Patrick Schlievert, and were remarkably effective at protecting rabbits from the lethal effects of the toxin.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Microbiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Buonpane, Rebecca Ann

Contributors dc:contributor

• Kranz, David M.

• Health Sciences, Immunology

Language dc:language

eng

Identifier

(MiAaPQ)AAI3250214

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/86690