# Project 3: T Cells

> **NIH NIH U54** · STANFORD UNIVERSITY · 2020 · $939,232

## Abstract

PROJECT 3: SUMMARY
COVID-19 is currently a global pandemic, but human T cell responses contributing to the quantity and quality of
SARS-CoV-2 specific antibodies, or acting by cytotoxic mechanisms on infected cells, remain poorly understood.
In this U54 Project, we will study virus-specific T cell immunity in the blood as well as the respiratory mucosal
tissues where the virus is likely to initiate infection. We will also compare responses to natural infection with
those generated by a peptide-based vaccine in early clinical trials, and in other vaccines approved during this 5-
year study. Our groups have previously developed a suite of innovative, high-throughput technologies and
computational algorithms to enable the analysis of TCR alpha beta sequences, transcriptional profiles, and
epigenetic states in primary T cells from human samples, providing a comprehensive view of T cell specificity
and molecular phenotype. We hypothesize that a critical component of immunity to SARS-CoV-2 is the antigen-
specificity, phenotype, and epigenetic durability of the T cell response, and the goal of this study is to measure
these components using high-throughput genomic tools to inform clinical profiles of protective immunity and the
design of effective vaccination strategies. In the first aim, we will build a comprehensive database of  TCRs
specific for SARS-CoV-2 and its variants to identify private and shared TCR specificities associated with disease
response and immunity. In the second aim, we will pair TCR specificities with transcriptional and epigenetic
phenotypes in SARS-CoV-2-specific T cells to identify immunotypes of the virus-specific T cell response. In the
third aim, we will investigate the role of epigenetic changes due to X chromosome inactivation in lymphocytes in
sex bias in COVID-19 immunity. We will pursue these aims in the context of several large patient cohorts of
COVID-19 patients, convalescent donors, and healthy subjects developed by the Clinical Virology Core, and all
T cell response data will be integrated with serology and B cell measurements in collaboration with Projects 1
and 2. Altogether, our studies will guide efforts to understand: (1) the diversity and specificity of antigen-specific
T cell responses in COVID-19 patients, (2) the phenotypes and durability of T cell memory in recovered
individuals, (3) relationships between T and B cell responses to SARS-CoV-2, and (4) T cell responses
stimulated by vaccination compared to natural infection.

## Key facts

- **NIH application ID:** 10222107
- **Project number:** 1U54CA260517-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Mark Morris Davis
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $939,232
- **Award type:** 1
- **Project period:** 2020-09-23 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10222107

## Citation

> US National Institutes of Health, RePORTER application 10222107, Project 3: T Cells (1U54CA260517-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10222107. Licensed CC0.

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