# Mechanisms of peripheral induction of T-cell tolerance

> **NIH NIH P01** · UNIVERSITY OF MINNESOTA · 2020 · $2,182,594

## Abstract

Summary
This application requests continued support for a long-standing P01 project on peripheral tolerance. This has
been a highly productive P01 that provided mechanistic insight about clonal deletion and anergy. These
discoveries were made through technical innovation in how to identify and manipulate self-antigen specific T
cells using pMHC tetramers. Based on preliminary data suggesting that mice with normal microbial experience
have strikingly altered immunity compared to specific pathogen free mice, we propose to focus in the next
period on understanding tolerance in the face of diverse pathogen experience, which is the reality for wild
animals and humans. The program includes five projects that will focus on distinct but complimentary aspects
of tolerance: natural MHCII-bound self epitope discovery, polyclonal anergic cells, type I interferons, non-
deletional CD8+ T cell tolerance, and hybrid self-peptides. The five investigatorial teams propose a strongly
synergistic plan to build a comprehensive understanding of physiologic T cell tolerance mechanisms that
operate in the face of normal microbial experience, and to continue to develop tools that have a broad impact
as we do so. The project includes three core facilities to enhance research productivity: 1) a mouse core to
facilitate and standardize research on mice bearing a diverse pathogen load, 2) a human tissue core to
facilitate the immunological analysis of multiple human tissues, not merely peripheral blood, and 3) an
administrative core to carry out activities that enhance the synergy and productivity of the group.

## Key facts

- **NIH application ID:** 9994812
- **Project number:** 5P01AI035296-26
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Kristin A. Hogquist
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,182,594
- **Award type:** 5
- **Project period:** 1997-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994812

## Citation

> US National Institutes of Health, RePORTER application 9994812, Mechanisms of peripheral induction of T-cell tolerance (5P01AI035296-26). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9994812. Licensed CC0.

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