# GENETIC STUDIES OF HUMAN IMMUNE RESPONSE

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1993 · $432,733

## Abstract

The principal long-term goal of this research is to determine the molecular
genetic basis of human immune responsiveness to allergens.  Atopic allergy
will provide a particularly good model for our studies, since the doses of
most inhaled allergens are very low and immunologically limiting.  We will
study two aspects of the immunogen-etic control:  the determination of
specific immune responsiveness by HLA-D and TcR genes; the regulation of
overall IgE antibody production, which we postulate to be controlled by
genes encoding certain lympho-kines, lymphokine receptors and/or proteins
which bind to the lymphokine gene promoters or enhancers.

We will investigate the relationship between the DNA sequences of HLA-D-
region genes and specific IgE and IgG antibody responses toward several
ultra-pure allergens, focusing on responsiveness to minor ragweed
allergens, Amb V and Amb VI, where single major epitopes are recognized by
specific Class II molecules.  HLA-D associations to further allergens will
be investigated primarily as part of an international HLA and Allergy
study.  Experiments will involve antigen-specific human T-cell clones and
lines, including quantitation of lymphokine production and analysis and
sequencing of T-cell receptor (TcR) genes.  Based on TcR sequence
similarities in the T-cell clones, we will design specific oligonucleotides
to investigate the relationships of specific TcR gene sequences to
responsiveness or non-responsiveness to Amb V and Amb VI.

We will analyze the genetics of overall IgE responsiveness in 42 large
nuclear families and several selected extended pedigrees from these and
further families.  We will define a new atopy-associated phenotype, which
is based on a subject's ability to respond to a defined set of inhalant
allergens.  We will investigate the distribution of this phenotype in
population studies and its mode of inheritance by segregation analysis in
the families.  We will investigate linkage between the defined, novel IgE
Ab phenotype and polymorphic genetic markers in (or near) certain key
lymphokine and lymphokine receptor genes that are known to be important in
IgE regulation in vitro.  Genetic studies will be coordinated with cellular
immunologic studies that are designed to explore the molecular basis of IgE
regulation.

A unique asset for our studies is the availability of extensive
epidemiologic and laboratory computerized data, and multiple serum samples
and cells from two large populations of ca 500 and ca 400 subjects.
Furthermore, we will be analyzing 1000+ atopic subjects from a unique
international HLA and Allergy study, which is part of the 1991
Histocompatibility Testing Workshop.  We also have data and sera on 55
large families from the first two groups of subjects, and will collect
further epidemiologic data and leukocyte samples from these and other
families and extended pedigrees for genetic studies under this grant.

## Key facts

- **NIH application ID:** 3129554
- **Project number:** 5R01AI020059-11
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **SAM.gov UEI:** FTMTDMBR29C7
- **Principal Investigator:** DAVID GEORGE MARSH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $432,733
- **Award type:** 5
- **Project period:** 1983-04-01 → 1997-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129554

## Citation

> US National Institutes of Health, RePORTER application 3129554, GENETIC STUDIES OF HUMAN IMMUNE RESPONSE (5R01AI020059-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129554. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*