Shared αβ T Cell Receptor Usage in Lungs of Sarcoidosis Patients with Löfgren’s Syndrome1

Sarcoidosis is a granulomatous disease that primarily affects the lungs and is characterized by an accumulation of CD4 + T cells in the bronchoalveolar lavage (BAL). Previous work has indicated that HLA-DRB1*03:01 + (DR3 + ) patients diagnosed with the acute form of the disease, Löfgren’s syndrome (LS), have an accumulation of CD4 + T cells bearing TCRs utilizing TRAV12-1 (formerly AV2S3). However, the importance of these α-chains in disease pathogenesis and the paired TCRβ chain remains unknown. This study aimed to identify expanded αβTCR pairs expressed on CD4 + T cells derived from the BAL of DR3 + LS patients. Using a deep-sequencing approach, we determined the TCRα and TCRβ chain usage as well as αβTCR pairs expressed on BAL CD4 + T cells from LS patients. TRAV12-1 and TRBV2 (formerly BV22) were the most expanded V region gene segments in DR3 + LS patients relative to control subjects, and TRAV12-1 and TRBV2 CDR3 motifs were shared between multiple DR3 + LS patients. When assessing αβTCR pairing, TRAV12-1 preferentially paired with TRBV2, and these TRAV12-1/TRBV2 TCRs displayed CDR3 homology. These findings suggest that public CD4 + T cell receptor repertoires exist amongst Löfgren’s syndrome patients and that these T cells are recognizing the putative sarcoidosis-associated antigen(s) in the context of HLA-DR3.