{"doi":"10.1084/jem.20250444","title":"Targeting infection-specific peptides in immunopeptidomics studies for vaccine target discovery","abstract":"Vaccine-elicited T cell responses can contribute to immune protection against emerging infectious disease risks such as antimicrobial-resistant (AMR) microbial pathogens and viruses with pandemic potential, but rapidly identifying appropriate targets for T cell priming vaccines remains challenging. Mass spectrometry (MS) analysis of peptides presented on MHCs can identify potential targets for protective T cell responses in a proteome-wide manner. However, pathogen-derived peptides are outnumbered by self-peptides in the MHC repertoire and may be missed in untargeted MS analyses. Here, we present a novel approach, termed PathMHC, that uses computational analysis of untargeted MS data followed by targeted MS to discover novel pathogen-derived MHC peptides more efficiently than untargeted methods alone. We applied this workflow to identify MHC peptides derived from multiple microbes, including potential vaccine targets presented on MHC-I by human dendritic cells infected with Mycobacterium tuberculosis (Mtb), finding that all Mtb peptides detected in the MHC-I repertoire derived from proteins exported by type VII secretion systems. PathMHC will facilitate antigen discovery campaigns for vaccine development.","journal":"The Journal of Experimental Medicine","year":2025,"id":519910,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":292650,"name":"Yuko Yuki","orcid":"0000-0003-1721-6003","position":1,"is_corresponding":false},{"id":37727,"name":"Mary Carrington","orcid":"0000-0002-2692-2180","position":2,"is_corresponding":false},{"id":91622,"name":"Bryan D. Bryson","orcid":"0000-0003-1716-6712","position":3,"is_corresponding":false},{"id":225709,"name":"Forest M. White","orcid":"0000-0002-1545-1651","position":4,"is_corresponding":false},{"id":716880,"name":"Owen Leddy","orcid":"0000-0002-3437-1956","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T02:49:23.618703Z","pmid":"40689854","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}