# Immune Tolerance in Non-Clonal Immune Systems

> **NIH NIH R37** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $534,731

## Abstract

Immunological tolerance regulates unwanted responses of B and T cells to self-tissue, reducing the chances of autoimmunity and focusing the immune response on foreign antigens. We review our progress in using transgenic models expressing superAgs that promote either central or peripheral B cell tolerance to study the genetics of the processes. We identified and verified a number of candidate genes whose mutation allowed B cell escape. We propose to find additional candidates, and evaluate existing validated targets in greater depth. To expand the identification of new candidate genes, we will focus on use of CRISPR mediated mutation or knockdown in hematopoietic stem cells. For the detailed mechanistic studies, we will examine in more detail proteins involved in ER stress and oncogenesis. The long-term goal of these studies is to develop a comprehensive understanding of all of the genetic components maintaining immune tolerance at these stages. This knowledge should facilitate treatment of autoimmune disorders and impact vaccine development.

## Key facts

- **NIH application ID:** 9849717
- **Project number:** 5R37AI059714-17
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** DAVID NEMAZEE
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $534,731
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849717

## Citation

> US National Institutes of Health, RePORTER application 9849717, Immune Tolerance in Non-Clonal Immune Systems (5R37AI059714-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9849717. Licensed CC0.

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