# Single cell RNA-Seq and clonal analysis of CD8+ T cells in MS

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $201,875

## Abstract

PROJECT SUMMARY/ABSTRACT
 Multiple sclerosis (MS) is an inflammatory demyelinating neurologic disorder thought to be caused by
immune-mediated injury against the central nervous system (CNS). The adaptive immune system, in particular,
is considered to be a central mediator of MS immunopathogenesis. CD8+ T cells are best known for their cytotoxic
function in viral and tumor immunity, yet compelling evidence suggests an important, but still largely unknown
role in MS. Deciphering which CD8+ T cells are relevant to the disease process and what unique characteristics
they possess is a critical hurdle to our understanding of MS.
 Studies analyzing the phenotype of T cells in the cerebrospinal fluid (CSF) of MS patients have indicated
increased levels of pro-inflammatory cytokines and activation status, however, these studies have focused on a
relatively narrow range of markers. Transcriptomics, using techniques such as RNA-Seq, provide an avenue for
studying a far vaster array of phenotypic markers. Single cell (sc)RNA-Seq is a relatively recently developed
technology that allows high throughput gene expression, thereby revealing the molecular profile of cells in
exquisite detail. To our knowledge, there have been no published single cell RNA-Seq studies on CD8+ T cells
in MS. Although prior studies of the intrathecal T cell receptor (TCR) repertoire have suggested greater CD8+ T
cell clonality compared to CD4+ T cells in MS, this has been limited to Vb analysis of bulk T cells. Thus, the true
clonal frequency of CD8+ T cells in the CSF is unclear. In addition, the lack of available paired TCR ab sequence
data precludes the future identification of T cell antigen specificity using unbiased antigen discovery platforms.
Very recently it became possible to combine scRNA-Seq and TCR ab sequencing.
 The objective of this proposal is to characterize specific CD8+ T cell sub-populations that are most likely
contributory to MS by measuring the clonal frequency and transcriptional profile by high throughput single cell
sequencing. It is hypothesized that clonally expanded CD8+ T cells from MS patients will have unique gene
expression profiles within the CSF compartment where disease-relevant cells are likely enriched. As an
extension of this unbiased approach, we will also perform single cell sequencing of newly identified myelin-
specific CD8+ T cells in MS patients, in order to determine their frequency and phenotype in the CSF. These
studies are expected to yield valuable insights into the features of CD8+ T cells that are likely relevant to MS
pathogenesis.

## Key facts

- **NIH application ID:** 9955174
- **Project number:** 5R21AI142186-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** SCOTT S ZAMVIL
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,875
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955174

## Citation

> US National Institutes of Health, RePORTER application 9955174, Single cell RNA-Seq and clonal analysis of CD8+ T cells in MS (5R21AI142186-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9955174. Licensed CC0.

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