# T CELL ANTIGEN RECEPTOR GENES IN AUTOIMMUNITY

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 1990 · $355,463

## Abstract

The pathogenesis and molecular basis of autoimmune diseases
such as systemic lupus erythematosus and rheumatoid arthritis
remain unknown.  These diseases are believed to be caused by
immunologic disturbances related to defects in tolerance
induction or immunoregulation, both profoundly affected by T
cells.  The T cell-dependence of both systemic and organ-specific
autoimmunity has been demonstrated conclusively in many
experimental systems and an important, perhaps pivotal, role for
specific autoreactive T cell clonotypes in initiating the disease
process is highly suspected.  Mouse autoimmune systems have
provided excellent models to study the role of T cell antigen
receptor (TCAR) genes in autoimmunity.  In this study, we will
attempt to further define the role of TCAR genes in
autoimmunity by assessing possible abnormalities in germline
TCAR gene repertoire and TCAR gene expression at prediseased
and diseased stages of mice with spontaneous lupus/arthritis
syndromes.  A collection of TCAR cDNA clones containing all, or
nearly all, the murine alpha, beta, gamma variable (V) region
sequences will be derived and used initially for definitive analysis
of the genomic composition and polymorphisms of these genes in
auto-immune-prone mice that correlate with disease.  Allelic
variations in germline-encoded TCAR genes could affect the
ability of a given strain's TCAR repertoire to respond to certain
antigens, and also affect its tendency to product autoreactive,
potentially pathogenic, T cell clonotypes.  Analysis of the
thymically-selected and expressed TCAR gene repertoires in
lymphoid organs of autoimmune mice will also be, initially at the
mRNA level, to identify V gene usage patterns characteristic of
autoimmune T cell populations, including clonal expansions or
deletions, and possible expression of unique or mutated TCAR
genes.  Once abnormal expression patterns are identified, anti-
"variotypic" (V region-specific) monoclonal antibodies will be
elicited and used to more precisely define, at the single-cell level,
aberrant clonotypes in lymphoid organs and lymphoid cell
infiltrates of afflicted tissues of autoimmune mice.  Anti-
"variotypic" antibodies will also be assessed for their in vitro and
in vivo effects on autoimmune responses and disease.  These
studies will provide a better understanding of TCAR repertoire
"shaping" during thymic selection and its possible role in the
development of autoreactive T cell clones.  Identification of
aberrancies in this central event is expected to have a significant
impact on our ability to molecularly define autoimmune diseases
and to devise specific and accurate means for their management.

## Key facts

- **NIH application ID:** 3159658
- **Project number:** 5R01AR039555-03
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **SAM.gov UEI:** PHZJFZ32NKH4
- **Principal Investigator:** Argyrios N Theofilopoulos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $355,463
- **Award type:** 5
- **Project period:** 1988-09-01 → 1993-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159658

## Citation

> US National Institutes of Health, RePORTER application 3159658, T CELL ANTIGEN RECEPTOR GENES IN AUTOIMMUNITY (5R01AR039555-03). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3159658. Licensed CC0.

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