Shared ?? TCR Usage in Lungs of Sarcoidosis Patients with Lofgren's Syndrome.

ABSTRACT: 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 using TRAV12-1 (formerly AV2S3). However, the importance of these ?-chains in disease pathogenesis and the paired TCR?-chain remains unknown. This study aimed to identify expanded ??TCR pairs expressed on CD4+ T cells derived from the BAL of DR3+ LS patients. Using a deep-sequencing approach, we determined TCR?- and TCR?-chain usage, as well as ??TCR 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 among multiple DR3+ LS patients. When assessing ??TCR pairing, TRAV12-1 preferentially paired with TRBV2, and these TRAV12-1/TRBV2 TCRs displayed CDR3 homology. These findings suggest that public CD4+ TCR repertoires exist among LS patients and that these T cells are recognizing the putative sarcoidosis-associated Ag(s) in the context of DR3.

SUBMITTER: Mitchell AM 

PROVIDER: S-EPMC5675165 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature