# GENETICS OF AUTOIMMUNITY

> **NIH NIH R01** · NATIONAL JEWISH HEALTH · 1991 · $216,020

## Abstract

We have identified an unusual allele of the T cell receptor Beta chain
locus in New Zealand White (NZW) mice.  This allele is distinguished by the
deletion of 8.8 kb of DNA containing CBeta1, DBeta2, and the entire JBeta2
cluster.  Thus, all NZW T cell receptor Beta chains are derived from a
single set of Beta chain gene segments (DBeta1, JBeta1 and CBeta2).
Interestingly, this deletion of T cell receptor Beta gene segments is
present in a strain known to contribute to lupus-like autoimmune diseases.

This grant proposes to fully characterize this unusual Beta chain allele
and to examine the consequences of its expression.  It is first planned to
clone and sequence the germline Beta chain gene complex from NZW mice.
This may elucidate the mechanism by which this allele was generated.

Mice congenic for the NZW Beta chain genes will be bred on the C57BL/6 and
BALB/c backgrounds.  Once these congenic strains are available, experiments
examining the repertoire of T cell specificities in these mice will be
performed.  The response to alloantigens (mutant H-2Kb gene products), and
conventional antigens (peptides of ovalbumin) will be investigated.  These
studies should allow us to examine the contribution of DBeta2 and JBeta2
gene segments to the T cell repertoire.

Since NZW mice contribute to the development of lupus-like autoimmunity in
NZB x NZW F1 animals, a straightforward genetic analysis [(NZB x NZW) F1 x
NZB backcross] will be undertaken to determine whether or not the NZW Beta
chain genes are involved in the pathogenesis of the F1 autoimmune disease.
If the NZW Beta chain genes are linked to development of lupus-like
disease, experiments are planned to elucidate the role of NZW Beta chain
genes in the disease process.  Mapping experiments are also planned to
examine the contribution of other NZW loci to NZB/NZW disease.

Finally, we will examine the DNA from patients with systemic lupus
erythematosus (SLE) to determine whether T cell receptor gene polymorphisms
are present in these individuals.

## Key facts

- **NIH application ID:** 3157916
- **Project number:** 5R01AR037070-06
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **SAM.gov UEI:** VLQKFEEJ3NE9
- **Principal Investigator:** EDWARD PALMER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $216,020
- **Award type:** 5
- **Project period:** 1986-04-01 → 1995-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157916

## Citation

> US National Institutes of Health, RePORTER application 3157916, GENETICS OF AUTOIMMUNITY (5R01AR037070-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3157916. Licensed CC0.

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