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The adaptive immune response plays a vital role in eliminating infected and aberrant cells from the body. This process hinges on the presentation of short peptides by major histocompatibility complex Class I molecules on the cell surface. Immunopeptidomics, the study of peptides displayed on cells, delves into the wide variety of these peptides. Understanding the mechanisms behind antigen processing and presentation is crucial for effectively evaluating cancer immunotherapies. As an emerging domain, immunopeptidomics currently lacks standardization-there is neither an established terminology nor formally defined semantics-a critical concern considering the complexity, heterogeneity, and growing volume of data involved in immunopeptidomics studies. Additionally, there is a disconnection between how the proteomics community delivers the information about antigen presentation and its uptake by the clinical genomics community. Considering the significant relevance of immunopeptidomics in cancer, this shortcoming must be addressed to bridge the gap between research and clinical practice. In this work, we detail the development of the ImmunoPeptidomics Ontology, ImPO, the first effort at standardizing the terminology and semantics in the domain. ImPO aims to encapsulate and systematize data generated by immunopeptidomics experimental processes and bioinformatics analysis. ImPO establishes cross-references to 24 relevant ontologies, including the National Cancer Institute Thesaurus, Mondo Disease Ontology, Logical Observation Identifier Names and Codes and Experimental Factor Ontology. Although ImPO was developed using expert knowledge to characterize a large and representative data collection, it may be readily used to encode other datasets within the domain. Ultimately, ImPO facilitates data integration and analysis, enabling querying, inference and knowledge generation and importantly bridging the gap between the clinical proteomics and genomics communities. As the field of immunogenomics uses protein-level immunopeptidomics data, we expect ImPO to play a key role in supporting a rich and standardized description of the large-scale data that emerging high-throughput technologies are expected to bring in the near future. Ontology URL: https://zenodo.org/record/10237571 Project GitHub: https://github.com/liseda-lab/ImPO/blob/main/ImPO.owl., (© The Author(s) 2024. Published by Oxford University Press.)