# Mapping the T cell receptor/antigen complex and identifying the genetic-based treatment in Sjogren’s syndrome

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $474,802

## Abstract

ABSTRACT
Sjögren's syndrome (SjS) is an autoimmune disease characterized by salivary and lacrimal gland dysfunction.
Although the clinical disease usually results in severe dry mouth and dry eyes, it can be systemic, affecting
other organs such as the lungs, skin, kidneys, bladder, and vagina. Like most autoimmune diseases, SjS
shows a sexual dimorphism with women affected >10-times more frequently than men, suggesting a strong
role for sex hormones in disease susceptibility and/or progression. One common feature of SjS in both
humans and animal models is mononuclear cells infiltrating salivary and lacrimal glands where they aggregate
into clusters referred to as lymphocytic foci. Our recent study has identified that glandular T helper (Th)1 and
Th17 cells of control and SjS patients expressed common T cell receptor (TCR)β variables (TRBV)3-1 and
TRBV20, whereas TCRα variable (TRAV)8-2 was uniquely expressed by Th1 cells of SjS patients. Using SjS
B6.NOD-Aec1/2 mice, we have shown that salivary Th1 cells of male mice selected for TRAV8 and TRBV16 in
Th1 and Th17 cells, whereas female Th1 cells selected for TRAV8, TRAV13D-2, and TRBV23. Other studies
attest our findings by identifying unique glandular TCRs in the humans and animal models of SjS. Our seminal
studies clearly imply that the clonal expansion of the effector T cells with the conserved TCRs is driven by
salivary gland (SG) cell antigens, and that autoimmune responses to SG cell autoantigens evidence a specific
loss of immunological self-tolerance. Therefore, the primary objectives of this application are to test the
specificity of the SjS TCRs with canonical SjS autoantigens and identify novel epitopes. Furthermore, using a
pioneering approach, we aim to block antigen presentation of autoantigens by pathogenic T cells as a therapy
to treat this debilitating disease. We hypothesize that “glandular pathogenic T cells possess oligoclonal
TCRαβ repertoires that react against conserved antigenic epitopes of autoantigens and that blocking
TCR activation by autoantigen-MHC complexes will prevent the development of SjS.” To test this
hypothesis, we will define the diversity of the TCRαβ gene repertoires for both mouse and human Th1,
Th2, and Th17 cells involved in SjS using single-cell microengraving technology (Aim 1); determine the
specificity of SjS TCRs with canonical SjS autoantigens and identify targets for recognition (Aim 2); and
examine the therapeutic effects of blocking pathogenic TCR activation by autoantigen-MHC complexes
using a rational structure-based approach (Aim 3). The significant aspect of this project is that it will
provide a broader understanding of the role SG autoantigens play in modulating pathogenic T cells and their
TCR repertoires. Additionally, results should establish the direction forward for generating and testing an
appropriate therapy for blocking antigen presentation. Interfering with specific antigen presentation processes
and pathogenic T cells will provid...

## Key facts

- **NIH application ID:** 9864060
- **Project number:** 5R01DE028544-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Cuong Q Nguyen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $474,802
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864060

## Citation

> US National Institutes of Health, RePORTER application 9864060, Mapping the T cell receptor/antigen complex and identifying the genetic-based treatment in Sjogren’s syndrome (5R01DE028544-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9864060. Licensed CC0.

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