# MURINE MODELS OF GENERALIZED AUTOIMMUNITY

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 1993 · $308,647

## Abstract

The primary roles of MHC molecules, T cell antigen receptors (TCR) and
certain lymphoaccumulation-inducing mutations (lpr,gld) in the
pathogenesis of murine lupus have been firmly established.  This
continuation application on murine models of generalized autoimmunity
will further address the molecular basis and biologic pathways by which
these genes contribute to the pathogenesis of this complex disorder.
The origin and mechanism of action of the autoimmunity
promoting/inducing lpr and gld double-negative TCR-alpha beta+ cells
will be pursued by assessing their thymic education, V-beta TCR gene
expression profiles, and ability to stimulate normal helper T cells to
produce T and B cell growth/differentiation-promoting lymphokines.  H-2
congenic lines of lupus mice will be developed to further define the
role of H-2 haplotypes in this disease, particularly of I-E and its
reactive V-beta clonotypes.  Our experiments to date of V-beta gene
expression profiles in lupus mice indicate disease/age-associated
expansions for T cell clones expressing certain V-betas, but their role
in disease pathogenesis and means of induction need to be determined.
Subtractive approaches with experimentally-induced tolerance-related
clonal deletions by neonatal injection of self- or foreign-superantigens
will be employed to address this issue.  Once disease-associated V-beta
clonotypes have been identified, attempts to develop new lupus
immunotherapies based on the elimination of such clones in adult mice
with anti-V-beta-specific antibodies, or their control by active
immunization with synthetic V-beta peptide vaccines, will be undertaken,
The recently established SCID mouse/human lupus model will also be used
to define human lupus-associated V-beta clonotypes and their autoimmune
potential.

## Key facts

- **NIH application ID:** 3155997
- **Project number:** 5R01AR031203-12
- **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:** 1993
- **Award amount:** $308,647
- **Award type:** 5
- **Project period:** 1983-04-01 → 1996-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155997

## Citation

> US National Institutes of Health, RePORTER application 3155997, MURINE MODELS OF GENERALIZED AUTOIMMUNITY (5R01AR031203-12). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155997. Licensed CC0.

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