Minelva Nanton

E-mail: nanto001@umn.edu

Thesis advisor: Stephen McSorley

Year entered: 2006

Degree received:
B.S., Biochemistry, SUNY Binghamton, Binghamton, NY 2005

Honors and awards:
DOVE Fellowship 2006

Thesis research:
Typhoid fever, caused by Salmonella enterica serovar typhi, is a major health concern in developing countries affecting 21 million people and killing 200,000 each year. It is well known that CD4+ T-cell responses are essential to clear a primary and secondary challenge with Salmonella. A well-established mouse model of typhoid has been used to study typhoid fever, in which mice susceptible to Salmonella enterica serovar typhimurium infection develop a typhoid-like disease. The CD4+ T-cell response to Salmonella typhimurium has primarily been studied using an adoptive transfer system in C57BL/6 mice. SM1 T-cells, monoclonal T-cell receptor (TCR) transgenic cells specific for a Salmonella typhimurium flagellin epitope, expand rapidly after live attenuated infection. SM1s do not persist past ten days, however, despite persistence of infection for at least 30 days. This phenomenon also occurs with transgenic CD4+ T-cells of other specificities during live infection. Therefore, an alternative method is required to study Salmonella-specific memory CD4+ T-cell responses. Using a flagellin peptide:Major Histocompatibility Complex II (pMHCII) tetramer, we have shown that endogenous, memory CD4+ T-cells specific for Salmonella flagellin peptide can be tracked in the spleen well past clearance of primary intravenous infection. My thesis project is to use this pMHCII tetramer technology to track memory CD4+ T-cells of multiple specificities following oral infection with S. typhimurium. I will be testing the hypothesis that Salmonella proteins highly expressed in the intestines of mice will elicit a CD4+ T-cell response necessary for B-cell help and antibody production in the intestinal mucosa, whereas Salmonella proteins highly expressed during the intracellular, systemic phase of infection will be important in priming CD4+ T-cell response necessary for clearing disseminated infection.