# STRUCTURE AND FUNCTION OF THE I REGION GENES

> **NIH NIH R01** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 1993 · $281,646

## Abstract

The major histocompatibility complex class II antigens have as one of their
primary functions the presentation of antigen to T helper cells.  The
expression of these proteins in the proper cells, and at the proper time,
is critical for the effective functioning of the immune system.  Our
primary interest is to examine how the genes coding for the MHC class II
antigens are regulated in both a cell specific manner and by cytokines.
Central to the regulation of these genes is the assembly of transcription
factors on the cis-acting elements located upstream of the genes.  In order
to better understand how these factors work, we propose to identify and
characterize the transcription factors involved in MHC class II gene
expression.

The initial goal will be to identify DNA binding proteins that bind to the
upstream region of the MHC class II gene, I-Abeta.  Because of the low
quantities of these proteins in cells, we have designed several approaches
to clone the genes for these DNA binding factors.  Once the genes have been
cloned, we will be able to generate sufficient quantities of protein for a
more detailed characterization of the proteins.  Basically, we would like
to know if these DNA binding proteins reflect the transcriptional activity
of the I-Abeta gene.  Possible changes to be investigated include the
splicing pattern of the genes and the phosphorylation status of the
proteins.  Any change found will be tested for its influence on
transcription.

It is likely that there are proteins that associate with the DNA binding
proteins via protein-protein interactions.  A second goal of ours will be
to identify these types of proteins.  The presence or absence of a
particular protein in cells that express MHC class II genes may provide new
ideas on how the class II genes are regulated.  If we see a protein
expressed only in cells that express class II genes, this protein will be
an excellent candidate for further characterization.

We also propose to study the expression of MHC class II genes in patients
with a deficiency in MHC class II expression.  It is possible that the
deficiency has its basis in a transcription factor.  We will begin this
study by examining the genes for the DNA binding proteins we have
characterized for any defects.  A mutation in the activation domain of one
of these proteins may be sufficient to alter drastically the expression of
the class II gene.

Finally, we will test various I-Abeta constructs in transgenic mice.  The
design of these experiments is to identify new cis-acting elements that may
be important for the developmentally regulated expression of the I-Abeta
gene.

## Key facts

- **NIH application ID:** 3129707
- **Project number:** 5R01AI020194-08
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **SAM.gov UEI:** PHMKYKKJLQS1
- **Principal Investigator:** RICHARD A MAKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $281,646
- **Award type:** 5
- **Project period:** 1984-04-01 → 1997-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129707

## Citation

> US National Institutes of Health, RePORTER application 3129707, STRUCTURE AND FUNCTION OF THE I REGION GENES (5R01AI020194-08). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3129707. Licensed CC0.

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