Title

Temporal and spatial distribution of antigen following respiratory viral infection

Date of Completion

January 2010

Keywords

Health Sciences, Immunology

Degree

Ph.D.

Abstract

Memory CD8 T cells generated by vaccines can be important for the prevention of viral infections; however, our understanding of the factors which contribute to the generation of CD8 T cell memory remains unclear. As is often the case, studying the immune response to natural infections provides valuable insight into T cell memory generation, which could then translate into the development of more effective T cell-based vaccines. To this end, we studied the kinetics and distribution of antigen presentation and the generation of a CD8 T cell response following influenza virus (IAV) and vesicular stomatitis virus (VSV) infections. The threat of new human IAV pandemics is a constant concern, which may be alleviated by the generation of broadly protective CD8 T cell-based vaccines. VSV, on the other hand, does not normally infect humans but has emerged as an extremely effective vaccine vector and could form the basis of new vaccines for diseases that are ineffectively controlled by current formulations. ^ To study the process by which memory CD8 T cells are generated following IAV infection we tracked the recruitment and activation of naive virus specific CD8 T cells in the draining lymph nodes (dLN) of the respiratory tract. We observed early indications of antigen encounter by cells in the dLNs; however, we also observed evidence of antigen encounter within the spleen. Thus it seems that, in a model of respiratory influenza infection, virus-specific CD8 T cells are generated in both the spleen and the dLNs. Antigen presentation in the spleen may therefore serve as a mechanism to ensure the involvement of a greater proportion of the naive virus-specific CD8 T cell repertoire in the immune response to a localized infection. Furthermore, we made the novel discovery that persistent presentation of viral antigen occurs for several weeks following IAV and VSV infection. Vaccines developed to mimic this persistent antigen presentation may therefore be more effective at generating large numbers of memory CD8 T cells than current vaccine formulations. ^