# GENETICS OF THE RESPONSE OF SELF-ANTIGENS

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1989 · $166,291

## Abstract

The long term goals of this project are to delineate the mechanisms
of autoimmune disease.  The murine experimental autoimmune
thyroiditis model of an organ specific autoimmune disease will be
used in this study.  There are two specific aims in this proposal.

1.  During organ specific autoimmune disease, self-tolerance is
lost and autoantibodies to indiginous antigens arise through, as
yet, an unknown mechanism.  There are two possible pathways through
which auto Ab may arise.  In the germline immunoglobulin variable
gene repertoire, there exist autoreactive V genes.  Pathologic
autoantibodies may be derived from these autoreactive, germline
encoded V genes.  Alternatively, autoreactive antibodies could
arise from non-autoreactive germline V genes as a result of post-
immunization somatic mutation.  The first pathway could be
explained totally by a loss of immunoregulation without the need
of an antigen driven maturation process.  The second pathway would
necessitate an the presence of antigen to drive maturation,
however, the process may be initiated by a unrelated antigen.  We
therefore, plan to clone, using recombinant DNA technology, the V
genes of anti-mouse thyroglobulin (MTg) Ab developing during the
disease process.  The selection of V genes used will be compared
to that of "natural" Ab that are autoreactive with MTg.  The
results from these experiments could point to one these pathways
and give insight into the processes which induce autoimmune
disease.

2. In the EAT model, disease can be easily induced by immunization
with mouse thyroglobulin.  The specific determinants involved in
this induction process are not known.  By chemical or enzymatic
cleavage of MTg, we propose to define specific peptide sequences
which are pathogenic or which can induce protective
immunosuppression.  Using the DNA probes derived from the amino
acid sequence of these peptides, the location of these sites within
the MTg molecule will be determined.  Furthermore, we will attempt
to distinguish determinants associated with development of disease
from those which are involved in inducing autoantibody production
alone.  These finding would further our understanding of the nature
of autoantigenic determinants.

## Key facts

- **NIH application ID:** 3156062
- **Project number:** 5R01AR031632-06
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **SAM.gov UEI:** FTMTDMBR29C7
- **Principal Investigator:** Noel R. Rose
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $166,291
- **Award type:** 5
- **Project period:** 1983-09-01 → 1991-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156062

## Citation

> US National Institutes of Health, RePORTER application 3156062, GENETICS OF THE RESPONSE OF SELF-ANTIGENS (5R01AR031632-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156062. Licensed CC0.

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