# An integrated approach to T cell repertoire in aging

> **NIH NIH R56** · UNIVERSITY OF TEXAS AT AUSTIN · 2020 · $349,999

## Abstract

Abstract
It has been shown that aging significantly impact the T cell receptor repertoire. It is also known that CMV infection
has a profound impact on the immune system's composition and function, especially with respect to CD8+ T
cells. Study in mice showed that chronic bystander infection impairs the CD8+ T cell repertoire on both transition
from effector to memory T cells as well as the function of preformed memory CD8+ cells. However, whether
these occurs in humans that have a much larger T cell repertoire and more resistant to thymic output decrease
is not known. In addition, it is not known how aging and CMV infection impact the maintenance and function of
precursor T cells that may protect host from future infections. Further we showed that aging reduces the
frequency of high-affinity T cell in naïve precursor T cells. However, studying these in human is challenging,
especially if we would like to survey the landscape of antigen-specific T cells to all possible peptide epitope
bound to one type of HLA as a way to assess the completeness, functional competence, and the affinity
distribution of the T cells to all possible antigens for one protein or an organism. Thus, in the proposed study, we
will integrate several tools we recently developed to assess T cells from multiple angles, namely TetATCR-Seq
for linking of TCR sequences to hundreds of pMHC antigens at single cell level in a high-throughput manner,
high-throughput CytoSeq that interrogates the expression level of 400 genes in each of 50,000 single cells, and
iTAST that measure T cell receptor. We will use these tools in combination of a human tetanus, diphtheria, and
pertussis vaccine recall study to comprehensively study the completeness, functional competence, and the
affinity distribution of the precursor T cells to all possible HCV virus peptides and memory T cells to all possible
tetanus and diphtheria toxin peptides. Expected results will systematically evaluate the impact of aging and CMV
infection on the maintenance and function of antigen-specific precursor and memory T cells.

## Key facts

- **NIH application ID:** 9970386
- **Project number:** 5R56AG064801-02
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Ning Jenny Jiang
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $349,999
- **Award type:** 5
- **Project period:** 2019-07-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970386

## Citation

> US National Institutes of Health, RePORTER application 9970386, An integrated approach to T cell repertoire in aging (5R56AG064801-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9970386. Licensed CC0.

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