# Antigenic determinants of asthma-associated allergens for design of immunotherapy

> **NIH NIH R01** · INDOOR BIOTECHNOLOGIES · 2020 · $642,434

## Abstract

TITLE: Antigenic determinants of asthma-associated allergens for design of immunotherapy
PROJECT SUMMARY/ABSTRACT
House dust mite allergy is an important health problem worldwide, affecting up to 85% of asthmatic children,
and a risk factor for emergency room admission with asthma. Group 1 and 2 mite allergens account for more
than 50% of total house dust mite specific IgE reactivity in mite allergic patients. Recently, Der p 23 has also
been identified as a major mite allergen, but its contribution to the total house dust mite specific IgE is small.
Group 1 allergens are cysteine proteases that contribute to lung inflammation in asthma, whereas group 2
allergens are lipopolysaccharide binding proteins. Der p 2 has been reported to mimic a human structural-
homolog that activates the innate immune system through toll like receptors. Despite these important molecular
differences between proteolytic group 1 and non-proteolytic group 2, a high IgE prevalence of 83% to allergens
from both groups has been observed in mite allergic patients in the U.S. However, the IgE repertoire and
antigenic determinants associated with these two major allergens are not known. The main goal of this
project is to investigate the antigenic structure of both groups of mite allergens for the design of
immunotherapy. Allergen-specific IgE monoclonal antibodies (mAb) will be produced for the first time with the
correct pairing of the heavy and light chains as they occur in vivo, using hybridomas obtained from the fusion of
B cells from allergic donors with a myeloma partner that confers immortality. Allergens will be co-crystallized
with recombinant IgE antibody constructs. The key amino acids involved in IgE antibody binding will be
identified and modified. The specific aims are: 1) Isolation of IgE mAb specific for asthma-associated allergens
by hybridoma technology; 2) mapping of antigenic determinants on groups 1 and 2 dust mite allergens by X-ray
crystallography and analysis of IgE antibody binding epitopes; and 3) site-directed mutagenesis of IgE antibody
epitopes for expression of hypoallergenic mutants with T cell reactivity as candidates for immunotherapy. An
analysis of the association between mite allergen-specific IgE antibodies from the human repertoire and the
epitopes recognized by these IgE antibodies will be performed with the information obtained in the first two
aims. Aim #2 will generate experimental data sets of three-dimensional structures of B-cell epitopes, which are
currently missing in databases used for developing tools for B cell epitope prediction. Most importantly, this
project will define IgE antibody responses to mite allergens and will provide the structural basis for rational
design of hypoallergens. In Aim #3, IgE antibody binding to the epitope mutants will be analyzed by
immunoassays and cell mediator release assays, and T cell reactivity will be evaluated. Mutants will be
compared and hypoallergenic forms will be selected for the desig...

## Key facts

- **NIH application ID:** 10047486
- **Project number:** 2R01AI077653-10A1
- **Recipient organization:** INDOOR BIOTECHNOLOGIES
- **Principal Investigator:** MARTIN D. CHAPMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $642,434
- **Award type:** 2
- **Project period:** 2009-08-25 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10047486

## Citation

> US National Institutes of Health, RePORTER application 10047486, Antigenic determinants of asthma-associated allergens for design of immunotherapy (2R01AI077653-10A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10047486. Licensed CC0.

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