# TCR PARAMETERS OF TREG FUNCTION IN AUTOIMMUNITY

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $381,250

## Abstract

ABSTRACT
T cell receptor (TCR) dictates T cell fate decision during development, steady state/homeostasis, and antigenic stimulation
in periphery. Recent expansion of deep sequencing technologies has uncovered a previously underappreciated TCR
diversity within antigen specific T cell responses. TCR diversity suggests a potential for functionally diverse T cell
response where TCR parameters command T cell fate decisions: T helper lineage development, T cell activation, or T cell
development into a regulatory T cell lineage. In order to understand the implications of this diversity observed in TCR
repertoire studies, we need to combine such approaches with functional analysis of TCRs. We are proposing to utilize a
combination of technologically advanced approaches to dissect TCR parameters that control Foxp3+ T cell development
and function in autoimmunity.
Development of type 1 diabetes is driven primarily by self-reactive T cells, which specifically recognize and target insulin
producing beta cells for destruction. We have previously published that beta cell reactive TCRs vary in their ability to
induce accumulation of T regulatory cells (Tregs) in the pancreatic islets of mice. Multiple studies suggest that the
strength of the TCR signal leading to Treg selection, expansion, and survival is unique and distinct from T effector T
cells. However, functional implications of a unique Treg TCR repertoire, such as antigenic specificity, Treg accumulation,
function, and stability of their regulatory phenotype in autoimmune diabetes are largely unknown. We hypothesize that
distinct TCR repertoire of islet infiltrating Tregs has intrinsic functional differences. The proposed study will
systematically characterize TCR repertoire, function, and signaling characteristic of islet infiltrating Treg TCRs. We will
use TCR retrogenic approach in combination with cutting edge genetic mouse models to test the function of insulin
reactive Treg TCRs in single TCR and competitive environments in the presence or absence of insulin epitope. The
ultimate goal of this proposal is to uncover functional implications of Treg specific TCR parameters in autoimmunity.
Insights gained from this study may lead to a significant impact on our understanding of the mechanisms behind Treg
function and failure in autoimmunity, and reveal potential avenues to improve development or homeostasis of Tregs with
relevant antigenic specificities.

## Key facts

- **NIH application ID:** 9856966
- **Project number:** 5R01AI125301-05
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Maria Bettini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2017-03-20 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856966

## Citation

> US National Institutes of Health, RePORTER application 9856966, TCR PARAMETERS OF TREG FUNCTION IN AUTOIMMUNITY (5R01AI125301-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856966. Licensed CC0.

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