biostudies-literatureUnknown22(4)Levy REuropean Research CouncilIsrael Science FoundationMRAPosttranslational spliced peptides (PTSPs) are a unique class of peptides that have been found to be presented by HLA class-I molecules in cancer. Thus far, no consensus has been reached on the proportion of PTSPs in the immunopeptidome, with estimates ranging from 2% to as high as 45% and stirring significant debate. Furthermore, the role of the HLA class-II pathway in PTSP presentation has been studied only in diabetes. Here, we exploit our large-scale cancer peptidomics database and our newly devised pipeline for filtering spliced peptide predictions to identify recurring spliced peptides, both for HLA class-I and class-II complexes. Our results indicate that HLA class-I-spliced peptides account for a low percentage of the immunopeptidome (less than 3.1%) yet are larger in number relatiMolecular & cellular proteomics : MCP100519https://www.ebi.ac.uk/biostudies/studies/S-EPMC10119686biostudies-literatureLarge-Scale Immunopeptidome Analysis Reveals Recurrent Posttranslational Splicing of Cancer- and Immune-Associated Genes.PMC10119686Shmueli MDBartok OTernette NAlon MGumpert NCohen Shvefel SAlter Regev TMerbl YDayan-Rubinov MLevin YLevy RPaes WSamuels YfalseLarge-Scale Immunopeptidome Analysis Reveals Recurrent Posttranslational Splicing of Cancer- and Immune-Associated Genes.Posttranslational spliced peptides (PTSPs) are a unique class of peptides that have been found to be presented by HLA class-I molecules in cancer. Thus far, no consensus has been reached on the proportion of PTSPs in the immunopeptidome, with estimates ranging from 2% to as high as 45% and stirring significant debate. Furthermore, the role of the HLA class-II pathway in PTSP presentation has been studied only in diabetes. Here, we exploit our large-scale cancer peptidomics database and our newly devised pipeline for filtering spliced peptide predictions to identify recurring spliced peptides, both for HLA class-I and class-II complexes. Our results indicate that HLA class-I-spliced peptides account for a low percentage of the immunopeptidome (less than 3.1%) yet are larger in number relati2023-01-01T00:00:00Z2023 Apr2026-05-28T16:50:54.447Z2025-02-19T04:16:03.422ZS-EPMC101196863682812710.1016/j.mcpro.2023.100519