A global analysis of proteins modified by O-linked N-acetylglucosamine in activated human T cells
Abstract/Contents
- Abstract
- A cell-mediated immune response requires the activation of antigen-specific T cells, which occurs when the T cell receptor (TCR) binds to a specific peptide antigen in the context of an MHC molecule. Engagement of the TCR triggers an intracellular signaling cascade that culminates in the acquisition of T cell effector functions. The regulation of TCR signaling is accomplished largely through protein post-translational modifications, most notably tyrosine phosphorylation. In recent years, the glycosylation of serine/threonine residues by O-linked N-acetylglucosamine (O-GlcNAc) has gained attention as another post-translational modification involved in the regulation of cell signaling. Previous studies indicate that O-GlcNAc is important for T cell activation, but a detailed understanding of how O-GlcNAc functions in T cells, especially primary T cells, is lacking. Thus, the objective of this thesis was to explore how O-GlcNAc participates in the events of T cell activation with particular emphasis on defining what proteins are modified by O-GlcNAc in primary T cells. Chapter 1 provides a general introduction to the topics of T cell activation and O-GlcNAc. Chapter 2 describes my main thesis research, in which we show that T cell activation leads to an overall increase in O-GlcNAc levels, that the activity of O-GlcNAc transferase is important for T cell function, and that hundreds of proteins are modified by O-GlcNAc in T cells. Chapter 3 proposes future directions for this research. Overall, our results provide impetus for future studies on how O-GlcNAc regulates the proteins we found to be modified and how this regulation may go awry in metabolic conditions that disrupt O-GlcNAc levels. Chapter 4 details a separate project that resulted in the identification of T cell epitopes from dengue virus, which will aid in the rational design of vaccines.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2015 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Lund, Peder Jens |
|---|---|
| Associated with | Stanford University, Program in Immunology. |
| Primary advisor | Davis, Mark |
| Thesis advisor | Davis, Mark |
| Thesis advisor | Crabtree, Gerald R |
| Thesis advisor | Elias, Joshua |
| Thesis advisor | Sonnenburg, Justin, 1973- |
| Thesis advisor | Sunwoo, John B |
| Advisor | Crabtree, Gerald R |
| Advisor | Elias, Joshua |
| Advisor | Sonnenburg, Justin, 1973- |
| Advisor | Sunwoo, John B |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Peder Jens Lund. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2015. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2015 by Peder Jens Lund
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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