# MOLECULAR ANALYSIS OF P/ANTI-P

> **NIH NIH R01** · HOSPITAL FOR SPECIAL SURGERY · 1991 · $111,210

## Abstract

The ribosomal P protein antigens are perhaps the only specific
protein antigens in human and murine SLE about which the
structure, function, epitopes, and amino acid sequences are known.
Using the P/anti-P antigen/antibody systems, the following
questions will be addressed:  a) Are the P protein antigens in
patients' cells normal?  The primary sequence of the P proteins
will be analyzed by recombinant DNA techniques and possible
environmental alterations studied by two-dimensional gel
electrophoresis.  The effect of phosphorylation of the major
epitope on autoantibody binding will be measured.  b) Can
unmodified P proteins stimulate and drive anti-P production in
MRL/lpr and BALB/c mice?  Mice will be immunized with mouse
whole ribosomes and the antibody response to all ribosomal
proteins analyzed by immunoblotting and anti-P levels assayed by
ELISA.  c) Are T cells involved in antibody production and can a T
cell antigen be defined?  In vitro proliferation and expression of
activation antigens (Tac, Ia, MRL3) will be studied in peripheral T
cells after exposure to P proteins and several possible
manipulations (IL-2 supplementation, removal of T suppressor
cells).  Since only 15% of MRL mice produce anti-P, the role of T
cells in vivo can be tested by adoptive transfer of T and B cells in
anti-P positive and negative mice.  d) Can anti-P antibodies be
specifically suppressed in MRL mice?  MRL mice will be injected
with either peptide-IgG2a conjugates or P protein-polyethylene
glycol conjugates at the age of 3 months and anti-P antibodies
serially measured by the ELISA.  e) How diverse are anti-P and
anti-Sm antibodies at the genetic level and are they derived from
a unique "autoimmune" subset of B cells?  Monoclonal antibodies
will be made from the spleens of MRL mice positive for both anti-
Sm and anti-P, RNA will be isolated and sequenced.

To develop safe forms of immunotherapy, it is important to
understand whether autoantibody production is antigen-driven and
if so, why?  ((a) and (b) above).  If autoantibodies are driven by
antigen, then suppressive therapy ((d) above) is likely to work.  If
T cells are involved ((c) above), then anti-clonotypic therapy can
be used.  The tools are available for exploring the diversity of
autoantibody production at the genetic level ((e above).  Defining
the genes involved in autoantibodies against the P and Sm
antigens may lead to fundamental insights regarding B cell subsets
involved in autoimmunity.

## Key facts

- **NIH application ID:** 3158955
- **Project number:** 5R01AR038915-04
- **Recipient organization:** HOSPITAL FOR SPECIAL SURGERY
- **Principal Investigator:** Keith B. Elkon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $111,210
- **Award type:** 5
- **Project period:** 1988-07-01 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158955

## Citation

> US National Institutes of Health, RePORTER application 3158955, MOLECULAR ANALYSIS OF P/ANTI-P (5R01AR038915-04). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3158955. Licensed CC0.

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