# On the plasticity of Beta-cell antigen recognition by diabetogenic CD8 T cells

> **NIH NIH R03** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $152,500

## Abstract

Project summary
CD8 T cells play an essential role in T1D pathogenesis. They comprise the most abundant immune cell
population in patient islet infiltrates. In the non-obese diabetic (NOD) model of T1D, they are required for
diabetes development. The infiltration and retention of autoreactive T cells in islets is strictly dependent on
specific recognition of beta-cell antigens. Such self-recognition also determines diabetogenic CD8 T cell’s
cytotoxicity and ultimate killing of beta-cells. However, little is known about how CD8+ T cells recognize beta-
cell antigens. Over the past decade, we have used novel 2D assays to characterize T cell antigen recognition
in general, revealing 2D affinity and mechanical force as two defining kinetics parameters in determining T cell
responses. In the current proposal, we will apply these 2D methods to beta-cell antigen recognition by
autoimmune CD8 T cells and elucidate the underlying molecular mechanisms by single cell RNA sequencing.
Our preliminary data show that diabetogenic CD8 T cells can greatly change affinity and/or force of self-antigen
recognition depending on T cell maturation, activation, and disease status. We propose two specific aims to
test a central hypothesis that diabetogenic CD8 T cells bind to beta-cell self-antigens weakly to evade
tolerance mechanisms but can upregulate bond strength to drive disease. In Specific Aim 1, we will use our 2D
methods to characterize affinity and force of beta-cell antigen recognition by CD8 T cells throughout the course
of diabetes. In Specific Aim 2, we will use single cell transcriptome analysis to elucidate molecular mechanisms
that abnormally regulate beta-cell self-antigen recognition. The project will generate critical yet currently
missing information on beta-cell self-antigen recognition and inform novel intervention strategies that are
capable of specifically targeting diabetogenic CD8 T cells.

## Key facts

- **NIH application ID:** 10296309
- **Project number:** 1R03DK129982-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Baoyu Liu
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $152,500
- **Award type:** 1
- **Project period:** 2021-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10296309

## Citation

> US National Institutes of Health, RePORTER application 10296309, On the plasticity of Beta-cell antigen recognition by diabetogenic CD8 T cells (1R03DK129982-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10296309. Licensed CC0.

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