# GENETIC STUDIES OF HUMAN IMMUNE RESPONSE

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1991 · $356,728

## Abstract

The principal long-term goal of this work is to determine the
genetic factors which control human immune responsiveness.
Since the dosages of most inhaled allergens are immunogenically
limiting, allergy provides a particularly good model for this study.
We hypothesize that two principal immunogenetic factors control
allergic response:  HLA-linked loci which control specific
antibody responses and non-HLA-linked loci which regulate
overall IgE responsiveness.

To study HLA-linked control of immune response, our approach
will be to define associations between specific HLA types and
responsiveness to various well-defined ultrapure allergens in
populations, followed by HLA linkage studies in families.  Both
the family and population studies will include the use of allergen
immunotherapy with defined antigen doses.  The molecular basis
of the associations will be defined in terms of HLA-D region gene
sequences.  To investigate the regulation of total IgE level, which
is controlled by non-HLA-linked genes, our approach includes
genetic-epidemiologic studies and investigation of the role of
glycosylation-inhibiting factor (GIF/lipocortin) and glycosylation-
enhancing factor (GEF).

The prototype antigens for the specific immune response studies
are three species of ragweed Amb V homologues, where there is a
striking relationship between immune responsiveness and HLA-
DR2/Dw2 in all cases.  We will investigate the structural basis for
immune recognition of three Amb V homologues by sequencing
HLA-D-region genes of five different groups of subjects, who
have different immune response phenotypes to the Amb V
molecules, but the same HLA-DR specificity, namely DR2.
"Immune response clusters" toward 35 different allergenic
extracts, and their relationship with HLA type, will also be
studied.

We will continue genetic analyses of factors regulating total
serum IgE level, an important step in determining the genetics of
allergic disease.  Further studies will include:  1) computer
simulation of family data to investigate whether current
analytical methods are powerful enough to detect the presence of
an IgE-regulating gene; 2) investigation of possible genetic
heterogeneity in families to determine whether there is a subset
of families with a major gene for IgE level; 3) studies of the
genetics of GIF and GEF levels to determine their effect on IgE
regulation.

## Key facts

- **NIH application ID:** 3129553
- **Project number:** 5R01AI020059-09
- **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:** 1991
- **Award amount:** $356,728
- **Award type:** 5
- **Project period:** 1983-04-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129553

## Citation

> US National Institutes of Health, RePORTER application 3129553, GENETIC STUDIES OF HUMAN IMMUNE RESPONSE (5R01AI020059-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129553. Licensed CC0.

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