Molecular determinants of T cell receptor specificity and activation
Abstract/Contents
- Abstract
- Molecular diversity is a fundamental property of the adaptive immune system. T cells, via the T cell receptor (TCR), have defined rules of recognition where a TCR must recognize a peptide presented in the context of an MHC molecule (pMHC) -- also known as MHC restriction. This allows for the sensitive discrimination between 'self' and 'foreign' antigens. The essentially infinite potential combinations of TCRs, and pMHC ligands, combined with the necessity to have high sensitivity and specificity, have made understanding molecular mechanisms behind TCR recognition and activation a central question of immunology. The overarching theme and objective of this thesis is to interrogate the key molecular and genetic determinants of T cell receptor specificity and activation. In Chapter 2, the TCR V-gene usage bias is examined at the population level -- the results provide a refined framework for the genetic pre-disposition of MHC specificity by the TCR. In Chapter 3, I examine naturally occurring high-affinity but non-agonist TCR-pMHC interactions in order to isolate key determinants of T cell activation. Finally, in Chapter 4, I use protein engineering techniques to engineer a "surrogate co-receptor" to both potentiate low affinity TCR-pMHC interactions, and to examine the cross-reactivity landscape of TCR-pMHC interactions within a lower affinity regime. Overall, this work brings new mechanistic, and potential therapeutic insight into understanding this sensitive, specific, and diverse receptor-ligand interaction network.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Sibener, Leah Vivian |
|---|---|
| Associated with | Stanford University, Program in Immunology. |
| Primary advisor | Garcia, K. Christopher |
| Thesis advisor | Garcia, K. Christopher |
| Thesis advisor | Butte, M. (Manish) |
| Thesis advisor | Davis, Mark M |
| Thesis advisor | Jardetzky, Theodore |
| Advisor | Butte, M. (Manish) |
| Advisor | Davis, Mark M |
| Advisor | Jardetzky, Theodore |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Leah Vivian Sibener. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Leah Sibener
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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