Life Sciences Commons^™

Mechanisms Of Cross-Presentation By Cdc1s, Derek James Theisen

Arts & Sciences Electronic Theses and Dissertations

Classical dendritic cells (cDCs) are specialized antigen presenting cells that can be divided into distinct subsets based on the types of pathogens they respond to and the type of immune response they generate. The cDC1 subset is specialized in priming CD8 T cell responses through the process of cross-presentation. During cross-presentation, exogenous protein antigens are taken up by cDC1 and presented on MHCI molecules, allowing for the priming of CD8 T cells during conditions when DCs themselves are not directly infected. The ability to cross-present in vivo is unique to cDC1, and is essential for anti-viral responses and rejection of …

A Recombinant Virus And Reporter Mouse System To Study Chronic Chikungunya Virus Pathogenesis, Alissa Roxanne Young

Arts & Sciences Electronic Theses and Dissertations

Chikungunya virus (CHIKV) is an arthritogenic alphavirus that during acute disease causes fever as well as severe joint and muscle pain. Chronic joint and muscle pain persists in a significant subset of patients, yet we still have a poor understanding of what drives this chronic disease. While replicating virus has not been detected in the joints of patients with chronic arthritis or in various animal models at chronic time points, persistent viral RNA can be detected for months after acute infection.

To identify the cells that could be contributing to chronic CHIKV pathogenesis, we developed recombinant viruses that express Cre …

Viral Mhc Class I Evasion Affects Anti-Viral T Cell Development And Responses, Elvin James Lauron

Arts & Sciences Electronic Theses and Dissertations

Cytotoxic CD8+ T cells (CTLs) play a critical role in protective immunity against viruses, a fact underscored by the evolution of viral CTL evasion mechanisms. For instance, many viruses commonly target the major histocompatibility complex class I (MHCI) antigen presentation pathway to prevent CTLs from recognizing infected cells. A striking example of this is cowpox virus (CPXV), which interferes with MHCI antigen presentation through two distinct mechanisms. One mechanism of CPXV-mediated MHCI inhibition is to retain MHCI molecules in the endoplasmic reticulum (ER). The second mechanism is to prevent antigen peptide loading onto MHCI molecules. When combined these mechanisms result …