Analysis of kinetics parameters on T cell recognition to viral infection

T cell kinetics;Viral infection;Immune response

Jothikumar, Prithiviraj ; Zhu, Cheng Biomedical Engineering (Joint GT/Emory Department) Grakoui, Arash Lu, Hang Roy, Krishnendu Platt, Manu ; Zhu, Cheng

University:Georgia Institute of Technology

Department:Biomedical Engineering (Joint GT/Emory Department)

关键词: T cell kinetics;    Viral infection;    Immune response;   

Others  :  https://smartech.gatech.edu/bitstream/1853/58605/1/JOTHIKUMAR-DISSERTATION-2016.pdf

美国|英语

来源: SMARTech Repository

【 摘 要 】

T cell plays an important role in clearance of viral infections and development of memory population for a rapid immune response in the case of secondary infections. T cells utilize T cell receptor (TCR) to recognize viral antigens in the form of peptide major histocompatibility complex (pMHC) as its ligand. When viral mutations occur, TCR recognition is impaired for its ligand and in result, lowers immune cell lytic response. Conventionally, TCR binding kinetics to its ligands is linked to TCR binding propensity stemming from 3D assays, providing numerical values in relation to its strength. However, characterizing the interaction of viral variant peptides to TCR is poorly understood and providing a unique perspective in understanding the interaction provides potential solutions to vaccine development, especially for chronic viral infections. In this study, we characterize Cytomegalovirus (CMV)-specific T cell 2D effective binding affinity to both WT and viral variants. Additionally, we characterized to elucidate the importance of specific amino acids found on the peptide influences recognition, thereby potentially bridging gap to understand the mechanics of how specific recognition motifs influence functionality. As T cell gets activated following peptide recognition, multiple signaling pathways take place in order to invoke an effective functional output. To invoke such a response, T cells first translate from naïve to activated state and then returning to homeostasis over the course of an immune response. Although the entire process takes several days, how recognition dynamics is influenced in the context of viral clearance and how that leads into developing memory population has not been fully elucidated. To understand these phenomenon, we primarily evaluated a single transgenic T cell population over the course of an acute lymphocytic choriomeningitis virus (LCMV) viral infection to characterize and understand the dynamics of the T cell function and development that is influenced by organ compartmentalization. Our results highlight an important aspect on how TCR propensity is influenced by the microenvironments during viral clearance and in the occurrence of viral mutation, how characterizing TCR recognition provides new insights on impaired binding kinetic and functional profile.