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Post-Translational Modifications Modulate the HLA-DR3 Restricted Epitope Landscape of Sjögren's Associated
Danmeng Li1, Alexandria Voigt1, Cuong Q Nguyen1,2,3
1Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611, USA.
Medicina (Kaunas, Lithuania)
|June 26, 2026
Summary
Post-translational modifications (PTMs) can alter how Sjögren's disease (SjD) autoantigens are presented by HLA-DR3 molecules. PTM-mimic peptides may enhance T cell responses, offering potential therapeutic strategies for SjD.
Area of Science:
- Immunology
- Autoimmune Diseases
- Molecular Biology
Background:
- Sjögren's disease (SjD) is a chronic autoimmune disorder affecting moisture-producing glands.
- Untreated SjD can lead to systemic inflammation, organ damage, and increased lymphoma risk.
- The human leukocyte antigen (HLA) class II molecule HLA-DR3 is strongly associated with SjD susceptibility.
Purpose of the Study:
- To investigate the impact of post-translational modifications (PTMs) on Sjögren's disease autoantigen presentation by HLA-DR3.
- To explore the potential of PTM-mimic peptides in modulating T cell responses in SjD.
Main Methods:
- Utilized a computational framework to predict the binding of PTM-mimic peptides to HLA-DR3.
- Performed in-vitro experiments to validate computational findings.
- Analyzed full-length SjD-associated autoantigen sequences (Ro60, Ro52, La) for PTM-eligible sites.
Main Results:
- PTM substitutions at anchor positions generally reduced predicted binding affinity to HLA-DR3.
- Identified specific regions in Ro60, Ro52, and La with high PTM-eligible anchor site densities.
- Experimental validation showed PTM-mimic peptides enhanced T cell responses and HLA-DR3 binding.
Conclusions:
- PTMs play a role in shaping the immunogenicity of SjD autoantigens in an HLA-DR3-dependent manner.
- PTM-mimic peptides can alter autoantigen presentation and enhance T cell responses.
- These findings suggest potential therapeutic applications of PTM-mimic peptides for SjD.
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