# Contribution of antigen presenting cells to thymic negative selection

> **NIH NIH F30** · UNIVERSITY OF MINNESOTA · 2020 · $27,181

## Abstract

PROJECT SUMMARY/ABSTRACT
Selection of the T cell receptor (TCR) repertoire is essential for producing T cells that are tolerant to self-
antigens, but poised to defend the host against pathogens. Although this selection process is considered
effective at removing self-reactive T cells from the repertoire, the high incidence of autoimmune diseases
indicates that this process is not perfect. Thus, greater understanding of this process is needed to identify the
mechanistic failures that predispose to autoimmunity. Heterogeneous populations of antigen presenting cells
(APCs) in the thymus drive selection of the TCR repertoire. Strong TCR interactions with self-peptide–MHC
complexes presented by these APCs result in clonal deletion or differentiation into regulatory T cells (Treg),
whereas weak interactions produce the naïve TCR repertoire via positive selection. Despite the diversity in
APCs that facilitate thymic selection, little is known about how they contribute independently to this process.
Therefore, the aims proposed in this project are designed to clarify the respective contributions of distinct APC
subsets to clonal deletion and Treg induction. Specifically, the results from these studies will further the
understanding of central tolerance based on cell-specific differences in driving selection of the T cell repertoire.
Aim 1 will use cell type specific MHC ablation to determine how distinct APC subsets impact clonal deletion
and Treg differentiation at early and late stages in the thymus. Furthermore, the proposed experiments will
distinguish if specific APC subsets are better equipped to contribute to negative selection of autoreactive
thymocytes. Aim 2 will evaluate the spatial distribution of heterogeneous dendritic cell populations in the
thymus. This aim will provide important insight into how subset-specific localization may dictate tolerance to
non-overlapping antigens presented in the thymus. Collectively, these results will substantially contribute to the
understanding of how specific APC populations drive both clonal deletion and regulatory T cell development in
a non-redundant manner. Moreover, this application provides a rigorous, defined scientific framework to foster
the career goals outlined in this application for becoming a successful physician scientist.

## Key facts

- **NIH application ID:** 9983561
- **Project number:** 5F30AI131483-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Elise R Breed
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $27,181
- **Award type:** 5
- **Project period:** 2017-08-01 → 2021-05-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983561

## Citation

> US National Institutes of Health, RePORTER application 9983561, Contribution of antigen presenting cells to thymic negative selection (5F30AI131483-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983561. Licensed CC0.

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