Muaz Nik Rushdi

PhD Proposal Presentation

Date: Tuesday, July 19th, 2016

Time: 9:00 AM

Location: Petit Institute Suddath Room (1128)

Committee Members:

Cheng Zhu, PhD (Advisor, BME)

Antony Chen, PhD (Co-advsior, Peking University)

Lou Ann Brown, PhD (Emory University)

Melissa Kemp, PhD (BME)

Khalid Salaita, PhD (BME, Emory University)

Characterization of T cell receptor signaling in an oxidative microenvironment

Cytotoxic lymphocytes (CTLs) scan the body for pathogen-infected cells and eliminate them primarily by granule-mediated apoptosis. The specificity of this immune response is mediated by the T cell receptor (TCR) which propagates recognition of antigen to T cell activation. Significant advances in force microscopies and high-resolution imaging in the past decade have revealed details of TCR signaling, but mechanisms of its impaired signaling in pathologic states are relatively less cohesive. Indeed, adverse cellular environments high in reactive oxygen species (ROS), such as in cancer, asthma, and COPD, can limit CTL activity. By using antigenic epitopes cognate to transgenic TCRs, the objective of this proposal is to dissect the effect of hydrogen peroxide on TCR signaling in an exclusively cellular context to understand the dynamics of TCR triggering in a pathologic environment. Furthermore, this proposal will investigate the role of antioxidants in improving CTL function in the cases of impaired viral clearance in asthma and COPD.  Overall, this study focuses on characterizing kinetics of TCR signaling and CTL function as the CTL encounters a pathologic environment high in ROS using 2D binding assays, force microscopies, and TIRF imaging. Ultimately, this study aims to advance the fields of immunology and free radical biology.