Immunopeptidome profiling in pulmonary fibrosis provides a new platform for identifying therapeutic targets

Fibrosis is the common and final pathological outcome of many chronic diseases and is a significant unmet medical need. Changes in the peptide profile presented by major histocompatibility complex class I molecules (MHC-I) are important pathological signals in diseases. The identification of "new antigens" in fibrosis potentially helps understand the pathogenesis and the therapeutic target. Here, we show that characterizing the MHC-I immunopeptidome of pulmonary fibrosis tissues identifies a series of pathological MHC-I ligands, leading to the discovery of multiple "fibrosis-associated antigens (FAAs)". Notably, three MHC-I peptides from Tns3, Apbb2, and Maf effectively block pulmonary fibrosis progression when used as a therapeutic vaccine. This study shows that profiling the immunopeptidome in fibrotic disease provides a promising platform for identifying therapeutic targets.