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Analysis of kinetic parameters on T cell recognition to viral infection
Advisor:
Cheng Zhu, Ph.D. (Georgia Institute of Technology, BME)
Thesis Committee:
Arash Grakoui, Ph.D. (Emory University)
Hang Lu, Ph.D. (Georgia Institute of Technology, ChBE)
Manu Platt, Ph.D. (Georgia Institute of Technology, BME)
Krishnendu Roy, Ph.D. (Georgia Institute of Technology, BME)
Persistent viral infections, such as cytomegalovirus (CMV) infection, rarely cause symptoms, as it remains dormant in healthy individuals. On the other hand, 80% of the individuals infected with hepatitis C virus (HCV) develop liver damage. Both are persistent viral infections, but the latter develops into a serious outcome. Unlike CMV, HCV is more susceptible to mutation and this in part causes chronic development of the infection. Some mutation, however, results in similar effect as the wild type. Cytotoxic T cell expressing T cell receptors (TCR) plays a pivotal role in mediating the immune system by interacting with the viral antigen. The initial interaction between the two proteins determines whether to recognize or tolerate the antigen. Although it has been shown that mutations plays a role in viral recognition, the mechanism of interaction and kinetics behind the evasion has not been fully elucidated. In addition, T cells from different compartments are characterized by different marker expressions upon infection and not much has been characterized on the binding kinetics of the TCR from T cells acquired from different compartments.
Therefore, this study focuses on explaining the kinetics of antigen recognition of various viral epitopes to wild type antigen-specific CD8+ T cells mimicking viral infection using direct 2D binding assays such as biomembrane force probe (BFP) and micropipette adhesion frequency assay. As a result, this study aims to contribute advancing the field of virology and immunology.
