# Accelerated dissociation of IgE receptor complexes

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $463,198

## Abstract

Project Summary
IgE antibodies and receptors are important mediators of the allergic cascade, but may also provide distinct
functions in anti-tumor immunotherapy. IgE engages its high affinity IgE Fc receptor (FceRI) on mast cells and
basophils as well as a low affinity receptor (FceRII/CD23) expressed on B cells and epithelial cells. IgE binding
to FceRI sensitizes allergic effector cells to allergens and is very stable, with the complexes persisting for
months even in the presence of potent anti-IgE antibodies. We have developed approaches to rapidly
destabilizing IgE:FceRI complexes and desensitizing allergic effector cells using hybrid, bispecific IgG/DARPin
molecules that recognize two distinct epitopes on the IgE-Fc. Here in Aim 1 we will explore alternative
approaches to target and remove IgE:FceRI complexes from cell surfaces using novel bispecific anti-IgE
antibodies. In addition, we will use two anti-IgE antibodies that we have produced to gain greater insights into
the structure and dynamics of intact IgE. The IgE interaction with CD23 also mediates important biological
effects in B cells, together with CD21. Here, in Aim 2, we will use yeast display to evolve higher affinity variants
of CD23 for its ligands to enable structural studies of these complexes and to probe CD23-dependent
regulation of IgE production by B cells. Finally, in Aim 3, we seek to isolate and study new anti-FceRIa
antibodies using yeast display, to develop novel reagents for the FceRI-directed modulation of allergic effector
cell activities.

## Key facts

- **NIH application ID:** 10906355
- **Project number:** 5R01AI115469-07
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Theodore S Jardetzky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $463,198
- **Award type:** 5
- **Project period:** 2017-01-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906355

## Citation

> US National Institutes of Health, RePORTER application 10906355, Accelerated dissociation of IgE receptor complexes (5R01AI115469-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10906355. Licensed CC0.

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