Tracing T cell clonal responses to chronic antigen stimulation using single-cell T cell receptor sequencing approaches
Abstract/Contents
- Abstract
- T cells play a central role in the immune response, protecting the host against immune challenges while maintaining self-tolerance. During acute infection, naïve T cells are activated in response to antigen and differentiate into memory precursors and effector T cells. Upon antigen clearance, effector T cells undergo apoptosis while memory cells survive and persist as long-lived memory T cells that are ready in case of subsequent infection. In settings where antigen stimulation persists, as in chronic infections and cancer, T cell development is modulated, such as through the development of exhausted T cell states characterized by limited effector function and high sustained expression of inhibitory receptors. How T cell responses to chronic antigen stimulation develop and are maintained are not well understood, especially at the level of individual T cell clones. Recently, the development of single-cell genomics technologies has enabled high-resolution profiling of the T cell compartment at the clonal and phenotypic levels. In particular, the ability to sequence the T cell receptor (TCR) of individual cells in parallel with gene expression allows for the dissection of the TCR repertoire in the context of cell states and finer interrogation of T cell clonal dynamics. Here, we dissect various aspects of the T cell response to chronic antigen stimulation by tracing clones using TCR sequencing methods. First, we demonstrate that CD4 T cell responses are maintained during chronic viral infection by a memory-like progenitor population. Then, we profile the T cell response to immune checkpoint blockade and characterize the regional distribution and cell states of T cell clones within the tumor, lymph nodes, and peripheral circulation of patients with lung cancer. Altogether, this work demonstrates how clonal tracing through single-cell TCR sequencing technologies and computational approaches can be leveraged to uncover features of T cell responses to chronic infection and cancer, and how this approach can be extended to other settings of immune challenge.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Pai, Joy |
|---|---|
| Degree supervisor | Satpathy, Ansuman |
| Thesis advisor | Satpathy, Ansuman |
| Thesis advisor | Curtis, Christina |
| Thesis advisor | Davis, Mark |
| Thesis advisor | Jerby, Livnat |
| Degree committee member | Curtis, Christina |
| Degree committee member | Davis, Mark |
| Degree committee member | Jerby, Livnat |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Department of Microbiology and Immunology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Joy Ann Pai. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/fp539yy0187 |
Access conditions
- Copyright
- © 2023 by Joy Pai
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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