• Login
    View Item 
    •   Athenaeum Home
    • University of Georgia Theses and Dissertations
    • University of Georgia Theses and Dissertations
    • View Item
    •   Athenaeum Home
    • University of Georgia Theses and Dissertations
    • University of Georgia Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    The role of CD8+ T cell immunodominance in control of experimental Trypanosoma cruzi infection

    Thumbnail
    Date
    2011-05
    Author
    Rosenberg, Charles Stephen
    Metadata
    Show full item record
    Abstract
    Trypanosoma cruzi infection drives the expansion of parasite-specific CD8+ T cells recognizing peptide epitopes encoded by trans-sialidase (TS) gene family members. The immunodominance of TS is remarkable; with up to 40% of all CD8+ T cells expressing T cell receptors recognizing the dominant TSKB20 and sub-dominant TSKB18 epitopes, these responses are among the strongest documented in any infection. However, mice fail to completely clear T. cruzi and subsequently develop chronic disease despite generating such highly focused T cell responses. Since T. cruzi’s genome encodes thousands of variant TS genes, we questioned the significance of these TS-specific CD8+ T cells. To determine the necessity of TS-specific CD8+ T cells for control of T. cruzi infection, we epitope-tolerized mice by injections of synthetic peptide epitopes. Mice tolerized to either the dominant or sub-dominant epitope, or both simultaneously, had transiently increased parasite burden though ultimately controlled acute infection, likely due to the activities of CD8+ T cells specific for unidentified parasite-derived epitopes. We hypothesized that these normally non-dominant CD8+ T cells could mediate long-term control of T. cruzi, so we developed transgenic mice expressing the TSKB20 or TSKB18 peptides as self-antigen to ensure central tolerance of peptide-specific CD8+ T cells. Recapitulating our previous findings, mice deleted of CD8+ T cells specific for TSKB20, TSKB18 or both peptides, were resistant to T. cruzi and developed functional effector CD8+ T cells. Mice deleted of the normally dominant CD8+ T cells controlled T. cruzi infection, but developed chronic infection and similar disease as their wild-type littermates. Though immunodomination by TS-specific T cells interferes with the development of responses targeting other parasite-encoded epitopes, deletion of the described dominant CD8+ T cells did not appear to enhance protective immunity nor change the outcome of infection. These data do not support a major role for TS-epitope immunodominance as a mechanism exploited by T. cruzi to promote the parasite’s persistence in the immune host, however, the data do indicate that strong responses against these TS-derived epitopes are non-essential. Furthermore, immunodominance by a particular CD8+ T cell population does not predict a critical role for that population in the control of T. cruzi infection.
    URI
    http://purl.galileo.usg.edu/uga_etd/rosenberg_charles_s_201105_phd
    http://hdl.handle.net/10724/27287
    Collections
    • University of Georgia Theses and Dissertations

    About Athenaeum | Contact Us | Send Feedback
     

     

    Browse

    All of AthenaeumCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    About Athenaeum | Contact Us | Send Feedback