T Cell Receptor Sharing in Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HP) is characterized by an excessive pulmonary T cell response after exposure to inhaled antigens. Antigen avoidance is the best treatment, but in most cases, an antigen cannot be identified. Profiling antigen-specific T cell responses in HP may provide a strategy to identify causative antigens. We used public RNA sequencing data and reconstructed T cell receptor (TCR) repertoires from bronchoalveolar lavage samples from patients with HP and idiopathic pulmonary fibrosis and healthy controls. After excluding TCR sequences likely to be related to common microbial exposures in patients with HP, we identified TCRs shared between patients with shared human leukocyte antigen alleles, indicating patients likely to have a common causative antigen. We also found clusters of identical and similar TCR clones in individual patients that are plausibly related to the causative antigens in those patients. These results establish the feasibility of profiling TCR repertoires to identify antigens in HP.