# STRUCTURAL AND FUNCTIONAL STUDIES OF I REGION VARIANTS

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 1988 · $141,620

## Abstract

We propose to comprehensively analyze the genetic polymorphisms of class II
genes in a collection of mouse strains which are homozygous for H-2
haplotypes derived from 5 separate sub-species of Mus.  The class II genes
and gene-products of these wild mouse-derived H-2 haplotypes will be
compared and they will be gouped into allelic families on the basis of
structural similarities.  The functional, structural, and genetic
properties of these families of class II gene alleles will then be studied
in detail.

The purpose of this study is to assess the evolutionary mechanisms
responsible for the production and maintenance of class II gene
polymorphisms.  The genetic mechanisms which generate class II gene
diversity will be studied by comparing the DNA sequences of structural gene
exons which have recently diverged.  This analysis will determine whether
copy mechanisms or gene conversion is involved in the generation of class
II gene diversity.  The presence of mutational "hot spots" in the I region
will be tested by the analysis of I region restriction site polymorphisms
with class II gene DNA probes.  Finally, the evolutionary stability of
specific class II alleles and class II gene haplotypes will be assessed by
comparisons of class II gene alleles prevalent in separate sub-species of
Mus.

The analysis of class II gene polymorphism in wild mice is a useful model
system for the analysis of class II genes in human populations.  Our
studies of wild mice suggest that a limited number of distally-related
allelic families of class II genes may predominate in natural populations.
Class II alleles in the same family encode A molecules with very similar
antigenic phenotypes and structural properties.  However, our functional
analysis of these closely-related alleles indicate that the minor
structural variations which distinguish their products are often capable of
stimulating strong mixed lymphocyte reactions and acute skin graft
rejections.  These observations in wild mice may be relevant to the poor
success rate of allograft survival between DR-identical, genetically
unrelated donor-recipient pairs in human transplantation studies.  We are
in the process of searching for minor structural variations in the class II
molecules of DR-identical individuals.

## Key facts

- **NIH application ID:** 3127574
- **Project number:** 5R01AI017966-08
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **SAM.gov UEI:** NNFQH1JAPEP3
- **Principal Investigator:** Edward K. Wakeland
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $141,620
- **Award type:** 5
- **Project period:** 1981-06-01 → 1989-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127574

## Citation

> US National Institutes of Health, RePORTER application 3127574, STRUCTURAL AND FUNCTIONAL STUDIES OF I REGION VARIANTS (5R01AI017966-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127574. Licensed CC0.

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