Using DNA mechanotechnology to relate T cell biophysics to immunological function

dc.contributor.advisor Salaita, Khalid
dc.contributor.author Kellner, Anna Victoria
dc.contributor.committeeMember Dreaden, Erik C.
dc.contributor.committeeMember Henry, Curtis J.
dc.contributor.committeeMember Thomas, Susan N.
dc.contributor.committeeMember Zhu, Cheng
dc.contributor.department Biomedical Engineering (Joint GT/Emory Department)
dc.date.accessioned 2024-01-10T18:39:20Z
dc.date.available 2024-01-10T18:39:20Z
dc.date.created 2022-12
dc.date.issued 2022-11-16
dc.date.submitted December 2022
dc.date.updated 2024-01-10T18:39:21Z
dc.description.abstract T cells survey the body for antigens by probing their environment through physical interactions. During these physical interactions, molecular-level forces transmitted through the T cell receptor (TCR) help discriminate antigenic tissue from self-tissue by prolonging TCR-antigen bonds and enhancing TCR signaling. This thesis describes the use of DNA mechanotechnology to help understand the role of these molecular-level forces in T cell function. First, we employed mechanotechnology to study the role of mechanics in PD1 receptor signaling. We found that the PD1 receptor is mechanically active, and that specific amino acid residues at the PD1-PDL2 interface are responsible for mechanical force transmission. Next, we used DNA mechanotechnology to study the role of plasma membrane cholesterol in TCR mechanics and signaling. We found that cholesterol depletion enhances TCR forces and triggering, and then hypothesized that this is due to cholesterol preventing TCR-cytoskeletal coupling. Finally, we used DNA mechanotechnology to investigate how the soluble microenvrionment tunes T cell function. We showed that the soluble microenvironment impacts cytoskeletal function and resulting T cell activation at the transcriptional and protein levels. We hypothesized that these changes were due to altered TCR mechanics and used DNA mechanotechnology to show that TCR forces are significantly altered by the soluble microenvironment. Importantly, we showed that TCR force modulation mirrored changes in the T cell functional response in both murine and human donor T cells. Our results suggest using “biomechanical biomarkers” to predict the outcomes of T cell-based immunotherapies prior to patient administration.
dc.description.degree Ph.D.
dc.format.mimetype application/pdf
dc.identifier.uri https://hdl.handle.net/1853/73016
dc.language.iso en_US
dc.publisher Georgia Institute of Technology
dc.subject T cell
dc.subject Immunology
dc.subject Immuno-oncology
dc.subject Mechanobiology
dc.subject DNA nanotechnology
dc.subject Obesity
dc.subject Cancer
dc.subject Biophysics
dc.subject Imaging
dc.subject TCR
dc.subject PD1
dc.subject Cholesterol
dc.title Using DNA mechanotechnology to relate T cell biophysics to immunological function
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor Salaita, Khalid
local.contributor.corporatename College of Engineering
local.contributor.corporatename Wallace H. Coulter Department of Biomedical Engineering
relation.isAdvisorOfPublication 473078da-e893-44af-8f0f-7a8cda93d9f5
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
relation.isOrgUnitOfPublication da59be3c-3d0a-41da-91b9-ebe2ecc83b66
thesis.degree.level Doctoral
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