A humanized transgenic mouse model for studying staphylococcal enterotoxin B

  • David, Chella S (PI)

Project: Research project

Project Details

Description

Staphylococcal enterotoxin B (SEB) is a polypeptide exotoxin produced by Staphylococcus aureus and
belongs to a family of microbial proteins called "superantigens". SEB, directly binds to MHC class II
molecules and potently activates both CD4+ and CD8+ T cells expressing certain T cell receptor (TCR) beta
chain variable region irrespective of their antigen specificities. As a result, SEB can cause a variety of clinical
illnesses ranging from self-limiting food poisoning to the more severe toxic shock syndrome, which can be
lethal. By virtue of its robust immunostimulatory property, SEB can also be used as agents of bioterrorism or
biological warfare. There is, however, a significant knowledge gap in our understanding of the
immunopathogenesis of SEB, largely attributed to a dearth of suitable animal models. Poor binding of SEB to
non-human MHC class II molecules results in ineffective activation of the immune system in common
laboratory animals and restricts their use in SEB research. Nonetheless, transgenic expression of HLA class
molecules in mice restores these defects and dramatically augments the immune response to SEB
delivered by several different routes. Faithful reproduction of human diseases and amenability to a variety of
immunological and genetic experimentations render HLA class II transgenic mice an ideal tool for studying
the in vivo biological effects of Staphylococcal enterotoxin B. Using this robust model, we propose to
thoroughly understand SEB-induced clinical syndrome and idetify effective theraeutic as well as preventive
interventions for SEB-induced clinical syndrome.
Specific Aim 1: Delineate the immunopathogenesis of the clinical syndrome resulting from airway exposure
to SEB;Specific Aim 2: Identify effective immunomodulatory agents for the treatment of SEB-induced clinical
syndrome; and Specific Aim 3: Design and evaluate novel vaccines specific for SEB.
The bacterial toxin, Staphylococcal enterotoxin B (SEB), causes many human diseases and can also be
used as a biological weapon. The mechanisms by which SEB causes diseases are poorly understood
because there are no good laboratory animal models. We propose to use the unique line of mice developed
by us (that express human molecules) to understand how SEB causes diseases and subsequently develop
effective drugs/vaccines for treating and preventing diseases caused by SEB.
StatusFinished
Effective start/end date9/30/079/29/08

Funding

  • National Institutes of Health: $226,650.00

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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