# GENETICS AND SEROLOGY OF H-2 (IR) LINKED IA ANTIGENS

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 1987 · $219,222

## Abstract

This proposal requests continued support for the genetic, serologic and
structural dissection of the genes and gene products coded by the I region
of the mouse major histocompatibility complex.  These Ia antigens (DR in
human) play a central role in immune regulation and thus are of major
importance in human disease.  During the next five years, emphasis will be
placed in the following areas: 1) gene conversion or copy mechanism has
been established as the major force through which genetic polymorphism
occurs for MHC genes.  We will screen for such occurrences for Ia genes by
making specific matings, surveying sublines of major inbred strains of mice
as well as utilizing crossreactions as indicators of gene conversion
events.  This would give us an insight into the frequency and mechanisms
underlining this very important event.  2) Using random fragment linked
polymorphisms with specific Ia gene probes, we will determine whether there
is a 'hot spot' in the E beta gene involved in recombination events.
Further, we will also determine the origin of the E alpha gene in several
new recombinants.  3) Molecular heterogeneity of Ia molecules will be
explored using several monoclonal antibodies in biochemical analysis.  Our
aims are to see whether there are additional Ia molecules present and
whether they are a result of newly identified Ia genes or other mechanisms
such as alternate splicing, and post-translational modifications.  We will
also determine the contribution of proteoglycans in generating Ia
heterogeneity.  4) We will continue our studies on the expression of Ia
antigens on T cell to determine why resting T lymphocytes do not express Ia
antigens.  We will look for soluble mediators which might turn on Ia
expression during T cell activation, possible role of methylation and
presence of tissue specific enhancer sequences.  5) We will initiate an
extensive program to produce trransgenic mice for Ia antigens.  We expect
this to be a difficult but worthwhile project.  6) We will continue our
serological and biochemical characterization of Ia antigenes by trying to
identify Ia on subpopulations of cells; we will try to identify new Ia
genes by reciprocal immunizations using new recombinant strains; and look
for quantitative differences in expression of Ia on B cells by FACS
analysis.  7) Even though not related to Ia, we will use our new L/D
recombinant to characterize the D region genes, their orientation,
boundaries and number of gene products.  Finally, we will continue our
service role of providing mouse strains and reagents to laboratories
throughout the United States and other parts of the world.

## Key facts

- **NIH application ID:** 3125867
- **Project number:** 5R01AI014764-11
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **SAM.gov UEI:** Y2K4F9RPRRG7
- **Principal Investigator:** CHELLA S DAVID
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $219,222
- **Award type:** 5
- **Project period:** 1977-09-01 → 1990-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125867

## Citation

> US National Institutes of Health, RePORTER application 3125867, GENETICS AND SEROLOGY OF H-2 (IR) LINKED IA ANTIGENS (5R01AI014764-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125867. Licensed CC0.

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