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

Fibrosis is a severe pathological outcome of many chronic diseases, yet the therapeutic potential of targeting the altered major histocompatibility complex (MHC) class I immunopeptidome remains largely unexplored. Here we characterized the MHC class I immunopeptidomes from both fibrotic foci of human idiopathic pulmonary fibrosis lung explants and bleomycin-treated mice, identifying a diverse repertoire of fibrosis-associated peptides. Parallel profiling of bleomycin-induced pulmonary fibrosis in mice enabled the computational prioritization of therapeutic targets. In vivo, therapeutic vaccination with three candidate peptides (MAF116–124, APBB270–78 and TNS3119–127) effectively mitigated fibrosis progression in bleomycin-treated mice. Furthermore, leveraging its evolutionary conservation, we found that MAF116–124 elicited specific human cytotoxic T lymphocytes that lysed human idiopathic pulmonary fibrosis-derived myofibroblasts and M2-like macrophages. This study indicates t­ ha­ t i­ mm­ un­ op­ ep­ tidome profiling provides a robust platform for discovering translatable a­nt­ifib­rotic i­mm­un­ot­he­ra­pies.

TO READ THE ARTICLE: https://www.nature.com/articles/s41590-026-02501-x