Comprehensive Mapping of Antigenic Landscapes in Sjögren’s Disease Using Enhanced T-Scan Technology

Mapping the full antigenic landscape of Sjögren's disease using T-Scan technology to identify the drivers of autoimmune T cell responses and enable targeted therapies.
Ongoing Sjögren’s Disease Systemic Diseases Adaptive Immunity Autoantigens Biological & Mechanistic Experimental Platforms & Models Human Cohorts Immune Profiling Immune Tolerance T Cell Biology Therapeutic Development Translational & Clinical

Funding Year: 2025

Project Overview

Sjögren's disease is a chronic autoimmune condition marked by immune attack on salivary and lacrimal glands, but the antigens driving this response remain poorly understood. This project applies enhanced T-Scan technology to perform the first unbiased, genome-wide screen of antigens recognized by both CD4+ and CD8+ T cells infiltrating affected tissue — including canonical human proteins, viral epitopes, and non-canonical self-antigens from cryptic genomic regions. By analyzing 40 prioritized T cell receptors from 30 SjD patients, the team will identify antigens driving autoimmunity and explore mechanisms such as molecular mimicry and immune tolerance breakdown, laying the foundation for biomarker discovery and antigen-targeted therapies.

Impact & Innovation

The first unbiased antigen map of Sjögren’s disease.

 

By screening canonical, viral, and cryptic self-antigens genome-wide using enhanced T-Scan, this project delivers the mechanistic foundation needed to design targeted therapies — from tolerogenic vaccines to T cell-based treatments — for SjD and beyond.

  • Explores non-canonical antigens and molecular mimicry as novel mechanisms of immune tolerance failure, addressing a critical gap in SjD pathogenesis research
  • Generates broadly applicable IP through the human non-canonical antigen library and T-Scan platform enhancements, with value across autoimmune research and therapy development
  • Advances the Consortium’s Shared Mechanisms Across Autoimmune Diseases pillar by mapping antigen-driven T cell responses in SjD in ways directly applicable to tolerance breakdown across autoimmune conditions
Research Approach

A framework designed for discovery

This project applies enhanced T-Scan technology to perform a comprehensive, genome-wide screen of T cell antigens in Sjögren’s disease, combining patient-derived T cell receptor analysis with broad antigen library screening to identify the drivers of autoimmune T cell responses in affected tissue.

Enhanced T-Scan platform screening of canonical human proteins, viral epitopes, and non-canonical self-antigens derived from cryptic genomic regions; analysis of 40 prioritized T cell receptors from 30 SjD patients; and mechanistic investigation of molecular mimicry and immune tolerance breakdown in salivary and lacrimal gland-infiltrating T cells.

T cell receptor sequences from CD4+ and CD8+ T cells infiltrating salivary and lacrimal gland tissue from 30 SjD patients, genome-wide antigen libraries including canonical, viral, and cryptic non-canonical self-antigens, and T-Scan screening datasets identifying disease-relevant antigenic targets.

Identification of the antigens driving autoimmune T cell responses in SjD, with translational goals including biomarker discovery and the design of targeted therapies such as tolerogenic vaccines and T cell-based treatments. The human non-canonical antigen library and T-Scan platform enhancements constitute novel and broadly applicable IP assets for autoimmune research and therapy development.

Investigators & Institutions

Powering the science

Principal Investigator

Mohammad Haj Dezfulian, PhD, Colton Consortium Member

Assistant Professor, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania

Colton Centers & Institutions

Colton Center for Autoimmunity at the University of Pennsylvania

Perelman School of Medicine