# EPSTEIN-BARR VIRUS AND AUTOIMMUNE DISEASE

> **NIH NIH R01** · SCRIPPS CLINIC AND RESEARCH FOUNDATION · 1989 · $326,762

## Abstract

Our belief is that autoimmune disorders are usually based upon
infectious agents, the autoimmunity often depending upon
molecular mimicry between virally-encoded proteins and normal
tissue proteins.  We will explore this concept in two diseases:
infectious mononucleosis (IM) and rheumatoid arthritis (RA).  In
IM, we have already established that IgM autoantibodies are
present, which react with numerous normal tissue proteins and
also with the glycine-alanine repeat in the Epstein-Barr virus
(EBV) encoded EBNA-1 protein.  In the IgM -- greater than IgG
isotype switch of anti-EBNA-1, which occurs in an unusually
delayed time scale, the antibodies lose their cross reactivities
with normal tissue proteins.  We will attempt to define
mechanisms for this loss of crossreactivity of the anti-EBNA-1
antibodies, exploring:  1) the possible role of anti-idiotypic
antibodies; 2) the nature of the T cell reactivity with EBNA-1
synthetic peptides and with fusion proteins representing the tissue
antigens; and 3) the phenotypes and functional potentials of the
reactive T cells.

In RA, we will explore T cell reactivities with EBV-encoded
antigens for two purposes:  1) to discern any possible disposition
of RA patients' lymphocytes as a group to react differently from
control lymphocytes with the peptides studied; and 2) to discern
whether B lymphocytes with given HLA Class II characteristics,
defined by classical typing sera, monoclonal antibodies, or family
studies, present the peptides differently from other B
lymphocytes, e.g. autoantigenically.  To determine whether T
lymphocytes activated in vivo as part of the RA disease process
exhibit anti-EBV (EBNA-1 or LYDMA) reactivity or autoimmune
reactivity, we will grow out synovial T lymphocytes in
interleukin-2 with intermittent anti CD3, clone them, and then
examine them against autologous B cells or synovial cells with and
without added EBV-associated peptides.  The presence in synovial
and salivary tissues of EBV encoded antigen or EBV DNA will be
sought by immunoperoxidase staining and by in situ hybridization,
respectively.

## Key facts

- **NIH application ID:** 3155158
- **Project number:** 5R01AR021175-12
- **Recipient organization:** SCRIPPS CLINIC AND RESEARCH FOUNDATION
- **Principal Investigator:** JOHN H VAUGHAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $326,762
- **Award type:** 5
- **Project period:** 1977-12-01 → 1993-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155158

## Citation

> US National Institutes of Health, RePORTER application 3155158, EPSTEIN-BARR VIRUS AND AUTOIMMUNE DISEASE (5R01AR021175-12). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155158. Licensed CC0.

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