# Impact of T cell receptor signaling on memory CD8+ T cell stemness

> **NIH NIH F31** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $53,974

## Abstract

ABSTRACT
CD8+ T cells' unique ability to sense and kill pathogen-infected and tumor cells makes developing human
vaccines designed to induce potent CD8+ T cell memory an important necessity. In this proposal, we explore the
roles of T cell receptor (TCR) signaling and peptide/MHC (pMHC) stability on generating memory CD8+ T cells.
Strong cognate antigen interactions induce robust primary effector responses and generate larger pools of
memory CD8+ T cells. However, whether the quality of TCR signaling and pMHC interactions can imprint distinct
CD8+ T cell memory programs is not well known. Prior studies state that differences in antigen stimulation do
not lead to functional differences, but our preliminary data suggest that the strength and the stability of pMHC
and TCR interactions do imprint functionally distinct cellular programs in resulting memory CD8+ T cells. Using
high-dimensional spectral flow cytometry, transgenic TCR and fluorescent reporter mouse models, and an
inducible lentiviral-based T cell gene editing approach, we will determine whether model epitopes with distinct
TCR signaling qualities can imprint distinct memory cell programs. In addition, we will characterize a subset of
memory CD8+ T cells that we propose are precursors to long-lived memory and test whether these cells confer
improved pathogen-specific protection. I am confident that I will successfully execute the proposed research and
training plans under the mentorship of Dr. Gregoire Lauvau with the support of our collaborators, Drs. Wenjun
Guo and Fabien Delahaye, experts in stem cell transduction and computational genomics, respectively. Findings
from our proposed study will contribute to a better understanding of memory CD8+ T cell formation and improve
rational design for CD8+ T cell-based vaccines and adoptive T cell transfer immunotherapies.

## Key facts

- **NIH application ID:** 10883564
- **Project number:** 5F31AI172421-02
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Erik Guillen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 5
- **Project period:** 2023-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883564

## Citation

> US National Institutes of Health, RePORTER application 10883564, Impact of T cell receptor signaling on memory CD8+ T cell stemness (5F31AI172421-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10883564. Licensed CC0.

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