Engineering Soluble, High Affinity Receptor Antagonists for Bacterial Exotoxins
Buonpane, Rebecca Ann
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https://hdl.handle.net/2142/86690
Description
Title
Engineering Soluble, High Affinity Receptor Antagonists for Bacterial Exotoxins
Author(s)
Buonpane, Rebecca Ann
Issue Date
2006
Doctoral Committee Chair(s)
Kranz, David M.
Department of Study
Microbiology
Discipline
Microbiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Immunology
Language
eng
Abstract
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.
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