# T cell epitopes in sarcoidosis

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $582,966

## Abstract

Project Summary
Sarcoidosis is a systemic granulomatous disorder of unknown etiology which 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 an acute form of sarcoidosis known as Löfgren’s syndrome, a correlation between the presence
of the HLA-DRB1*03:01 allele and expansions of lung CD4+ T cells expressing the T cell receptor (TCR) α-
chain variable (V) region Vα2.3 has been observed. These T cell populations are oligoclonal in nature,
suggesting their recruitment to the lung in response to conventional antigen. In addition, these T cell
expansions are compartmentalized to the lung and disappear with disease remission, underscoring their
importance in disease pathogenesis. We hypothesize that in HLA-DRB1*03:01 individuals with Löfgren’s
syndrome, Vα2.3-expressing CD4+ T cell clones accumulate and expand in the lungs in response to the
etiologic sarcoidosis antigen and recognize that antigen in an HLA-DRB1*03:01-restricted fashion. This
proposal harnesses the strengths of an international research team and focuses on a distinct cohort of HLA-
DRB1*03:01+ Swedish subjects with Löfgren’s syndrome in which two of the three components of the
trimolecular complex are known (i.e., HLA-DRB1*03:01 and Vα2.3-expressing CD4+ T cells). Using a single
cell RT-PCR approach, Aim 1 will characterize the αβTCR pairs expressed on CD4+ Vα2.3-expressing T cells
in the BAL of Löfgren’s syndrome patients and generate hybridomas expressing the TCRs of interest. The
second specific aim will determine the peptides that stimulate the CD4+ T cell hybridomas expressing disease-
relevant TCRs derived from Löfgren’s syndrome patients. The final aim will use HLA-DR3-peptide tetramers to
identify 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 prognosis. Thus, using innovative and novel
technology, we will address critical knowledge gaps in the etiologic T cell antigens involved in the initiation of
disease in patients with Löfgren’s syndrome, further advancing our understanding of the pathogenesis of this
disease. In addition, these results will lay the foundation for additional studies of sarcoidosis in the US.

## Key facts

- **NIH application ID:** 9932487
- **Project number:** 5R01HL136137-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Andrew P. Fontenot
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $582,966
- **Award type:** 5
- **Project period:** 2017-07-05 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932487

## Citation

> US National Institutes of Health, RePORTER application 9932487, T cell epitopes in sarcoidosis (5R01HL136137-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9932487. Licensed CC0.

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