Shared αβ TCR Usage in Lungs of Sarcoidosis Patients with Löfgren's Syndrome.

Angela M Mitchell, Ylva Kaiser, Michael T Falta, Daniel J Munson, Laurie G Landry, Anders Eklund, Maki Nakayama, Jill E Slansky, Johan Grunewald, Andrew P Fontenot

Journal of immunology (Baltimore, Md. : 1950) 2017 Oct 01

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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. Copyright © 2017 by The American Association of Immunologists, Inc.

Citation

Angela M Mitchell, Ylva Kaiser, Michael T Falta, Daniel J Munson, Laurie G Landry, Anders Eklund, Maki Nakayama, Jill E Slansky, Johan Grunewald, Andrew P Fontenot. Shared αβ TCR Usage in Lungs of Sarcoidosis Patients with Löfgren's Syndrome. Journal of immunology (Baltimore, Md. : 1950). 2017 Oct 01;199(7):2279-2290