# MODE OF ACTION OF H-LINKED IMMUNE RESPONSE (IR) GENES

> **NIH NIH R01** · JEWISH HOSPITAL OF SAINT LOUIS · 1990 · $198,129

## Abstract

The long term objectives of this project are to determine the mechanisms by
which H-2-linked immune response (Ir) genes regulate immune responses to T
cell dependent antigens.  Although the hypothesis that the Ia antigens are
the Ir gene products is widely accepted, it does not explain how Ia
antigens mediate the highly specific Ir gene functions.  Our previous
studies support the postulate that Ir gene control is the net result of the
stimulation of various regulatory helper and suppressor T cell subsets.
Thus, the specific aims of this proposal focus on the detailed
characterization of differences in regulatory T cell subsets between
responder and nonresponder mice.

Development of antibody responses by inbred strains of mice to the
synthetic polypeptides:  L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT)
and L-glutamic acid50-L-tyrosine (GT) and a panel of proteins comprised of
several insulin variants obtained from different species serve as model
systems.  Development of specific helper T cell clones and suppressor T
cell hybridomas as sources of homogeneous regulatory T cells will be
continued.  The mechanisms by which suppressor T cells inhibit responses
will be analyzed using soluble, antigen-specific suppressor factors and
suppressor-inducer factors.

The clinical importance of understanding precisely how Ir genes function is
supported by evidence that Ir genes also regulate immune responses in
humans.  Several organ-specific autoimmune diseases are associated with
certain haplotypes of the D/DR region of the HLA-complex suggesting that
this locus is analogous to the murine I region.  Thus, the role of Ir genes
in development of experimental autoimmune diseases in mice will be
investigated as a model system.

Once the biology of suppressor T cells is well understood, it should be
possible to produce suppressor factors to modulate indesirable immune
responses specifically.  Because it would not be feasible to design a new
factor for every disease and every individual, we will determine whether
specific factors can be targeted to neoantigenic determinants via an
antigen bridge.  If numerous responses can be suppressed with a single
factor, the therapeutic potential of suppressor factors would be very
promising.  Ultimately these studies might provide the basis to prevent
induction of anti-insulin antibodies in insulin-dependent diabetics and to
reverse autoimmune diseases with specific suppressor T cell factors.

## Key facts

- **NIH application ID:** 3125597
- **Project number:** 5R01AI013987-13
- **Recipient organization:** JEWISH HOSPITAL OF SAINT LOUIS
- **Principal Investigator:** JUDITH A KAPP
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $198,129
- **Award type:** 5
- **Project period:** 1977-04-01 → 1990-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125597

## Citation

> US National Institutes of Health, RePORTER application 3125597, MODE OF ACTION OF H-LINKED IMMUNE RESPONSE (IR) GENES (5R01AI013987-13). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125597. Licensed CC0.

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