# Neo-antigens and the function of HLA-DR alleles in autoimmune arthritis

> **NIH VA I01** · MEMPHIS VA MEDICAL CENTER · 2020 · —

## Abstract

Abstract
 The focus of this proposal is to identify the role of posttranslational modifications of proteins
and peptides in the development of an autoimmune T cell response. The hypothesis directing
these studies is that inflammation induces localized posttranslational modifications (PTM) of
proteins, and that these modifications induce epitope spreading by generating neo-epitopes
which become focal points of autoimmune T cell stimulation that perpetuate the autoimmune
disease. Recent clinical observations have implicated PTM proteins as potential autoantigens
in RA and other autoimmune diseases. The posttranslational modification of arginine to
citrulline has become a major focus of study in RA as the presence of antibodies to citrullinated
proteins has become a diagnostic for this autoimmune disease. Recently, antibodies to
homocitrulline, a PTM of lysine, have also been described. In our proposed studies, we will
use humanized mouse models that express HLA-DR1 or DR4 alleles which are associated
with susceptibility to RA, and study the role of PTM peptides in the development of
autoimmune arthritis. Through the experiments in this proposal we will gain new insight into
the evolution of an autoimmune T cell response mediated by these HLA-DR alleles and how
the PTM of autoantigens is involved in the generation and function of autoimmune T cells at
the site of inflammation. The studies in this proposal are focused on: a) the role of
posttranslational modifications of autoantigenic peptides in generating neo-epitopes that
stimulate T cells in autoimmune arthritis, b) the identification, specificity, and functional
phenotype of these PTM neo-epitope-specific CD4+ T cells that are found within the inflamed
arthritic joints, and c) the binding and presentation of the PTM peptides by RA susceptibility
alleles DR1 and DR4 and the role of the shared eptiope in the presentation of these peptides
to T cells.

## Key facts

- **NIH application ID:** 9863995
- **Project number:** 5I01BX003256-04
- **Recipient organization:** MEMPHIS VA MEDICAL CENTER
- **Principal Investigator:** Edward F Rosloniec
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-01-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9863995

## Citation

> US National Institutes of Health, RePORTER application 9863995, Neo-antigens and the function of HLA-DR alleles in autoimmune arthritis (5I01BX003256-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9863995. Licensed CC0.

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