Shared αβ TCR usage in lungs of sarcoidosis patients with Löfgren's syndrome

AM Mitchell, Y Kaiser, MT Falta, DJ Munson… - The Journal of …, 2017 - journals.aai.org
AM Mitchell, Y Kaiser, MT Falta, DJ Munson, LG Landry, A Eklund, M Nakayama, JE Slansky…
The Journal of Immunology, 2017journals.aai.org
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 α-chains in disease
pathogenesis and the paired TCRβ-chain remains unknown. This study aimed to identify …
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 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 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 among 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+ TCR repertoires exist among LS patients and that these T cells are recognizing the putative sarcoidosis-associated Ag (s) in the context of DR3.
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