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

• Published in: The Journal of immunology (1950) Vol. 199; no. 7; pp. 2279 - 2290
• Main Authors: Mitchell, Angela M, Kaiser, Ylva, Falta, Michael T, Munson, Daniel J, Landry, Laurie G, Eklund, Anders, Nakayama, Maki, Slansky, Jill E, Grunewald, Johan, Fontenot, Andrew P
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 01.10.2017
• Subjects: Acute Disease; Adult; Aged; Alveoli; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Bronchus; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Complementarity-determining region 3; Drb1 protein; Female; High-Throughput Nucleotide Sequencing; Histocompatibility antigen HLA; HLA-DRB1 Chains - genetics; HLA-DRB1 Chains - immunology; Homology; Humans; Lung - immunology; Lymphocytes; Lymphocytes T; Male; Middle Aged; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - immunology; Receptors, Antigen, T-Cell, alpha-beta - metabolism; Receptors, Tumor Necrosis Factor, Member 25 - genetics; Receptors, Tumor Necrosis Factor, Member 25 - immunology; Sarcoidosis; Sarcoidosis, Pulmonary - immunology; T cell receptors
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1700570

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.