Post-translational modifications reshape the antigenic landscape of the MHC I immunopeptidome in tumors.

Autor: Kacen A; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel., Javitt A; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel., Kramer MP; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel., Morgenstern D; De Botton Institute for Protein Profiling, Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel., Tsaban T; Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University, Jerusalem, Israel., Shmueli MD; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel., Teo GC; Department of Pathology, University of Michigan, Ann Arbor, MI, USA., da Veiga Leprevost F; Department of Pathology, University of Michigan, Ann Arbor, MI, USA., Barnea E; Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel., Yu F; Department of Pathology, University of Michigan, Ann Arbor, MI, USA., Admon A; Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel., Eisenbach L; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel., Samuels Y; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel., Schueler-Furman O; Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University, Jerusalem, Israel., Levin Y; De Botton Institute for Protein Profiling, Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel., Nesvizhskii AI; Department of Pathology, University of Michigan, Ann Arbor, MI, USA.; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA., Merbl Y; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. yifat.merbl@weizmann.ac.il.
Jazyk: angličtina
Zdroj: Nature biotechnology [Nat Biotechnol] 2023 Feb; Vol. 41 (2), pp. 239-251. Date of Electronic Publication: 2022 Oct 06.
DOI: 10.1038/s41587-022-01464-2
Abstrakt: Post-translational modification (PTM) of antigens provides an additional source of specificities targeted by immune responses to tumors or pathogens, but identifying antigen PTMs and assessing their role in shaping the immunopeptidome is challenging. Here we describe the Protein Modification Integrated Search Engine (PROMISE), an antigen discovery pipeline that enables the analysis of 29 different PTM combinations from multiple clinical cohorts and cell lines. We expanded the antigen landscape, uncovering human leukocyte antigen class I binding motifs defined by specific PTMs with haplotype-specific binding preferences and revealing disease-specific modified targets, including thousands of new cancer-specific antigens that can be shared between patients and across cancer types. Furthermore, we uncovered a subset of modified peptides that are specific to cancer tissue and driven by post-translational changes that occurred in the tumor proteome. Our findings highlight principles of PTM-driven antigenicity, which may have broad implications for T cell-mediated therapies in cancer and beyond.
(© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
Externí odkaz: