# T cell Epitope Discovery in Sarcoidosis

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2024 · $554,776

## Abstract

Project Summary
Sarcoidosis is a systemic granulomatous disorder of unknown etiology that affects the lung in greater than 90%
of cases. The disease is characterized by the accumulation of activated CD4+ T cells in the lung and other sites
of disease activity. Evidence suggests that these T cells are intimately involved in the pathogenesis of
sarcoidosis. In the previous version of this proposal, we identified lung CD4+ T cells from HLA-DR3-expressing
Löfgren’s syndrome (LS) subjects expressing related T cell receptors (TCRs) and determined that these TCRs
recognized peptides derived from NAD-dependent protein deacetylase (NDPD) expressed in a common airborne
mold species, Aspergillus nidulans. Using HLA-DR3-NDPD tetramers and IFN-γ ELISPOT, we validated those
findings and showed that a significantly greater number of NDPD-responsive CD4+ T cells exists in the lungs of
LS subjects; thus,we have identified a potential causative agent in the genesis of LS. This study of Swedish
subjects with LS serves as a “proof of concept” for the current renewal whose focus is to identify T cell epitopes
for CD4+ T cells derived from the lungs of sarcoidosis subjects expressing HLA-DRB1*11:01, the HLA allele
strongly linked to sarcoidosis in Caucasians and African-Americans in the US. Thus, we hypothesize that
expanded CD4+ T cells in the lungs of HLA-DRB1*11:01-expressing US sarcoidosis patients are
accumulating in response to etiologic sarcoidosis antigen(s) and recognize those antigens in an HLA-
DRB1*11:01-restricted fashion. This proposal harnesses the strengths of a multidisciplinary research team
and focuses on a sarcoidosis cohort in the US. Using a single cell RT-PCR approach, Aim 1 will characterize
αβTCR pairs expressed on CD4+ T cells derived from the lungs of US sarcoidosis patients and generate
hybridomas expressing disease-relevant TCRs. The second specific aim will determine the peptides that
stimulate the CD4+ T cell hybridomas expressing the TCRs of interest. The final aim will use functional assays
and HLA-DR11-peptide tetramers to identify and enumerate antigen-specific CD4+ T cells in the lungs of
sarcoidosis patients and determine if the frequency of these T cells can serve as a biomarker for diagnosis and/or
prognosis. Thus, using a novel yet proven scientific approach, we will address critical knowledge gaps in the
etiologic T cell antigens involved in the pathogenesis of sarcoidosis in US patients, further advancing our
understanding of this enigmatic disease.

## Key facts

- **NIH application ID:** 10908276
- **Project number:** 5R01HL136137-08
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** BRENT E PALMER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $554,776
- **Award type:** 5
- **Project period:** 2017-07-05 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908276

## Citation

> US National Institutes of Health, RePORTER application 10908276, T cell Epitope Discovery in Sarcoidosis (5R01HL136137-08). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10908276. Licensed CC0.

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