Understanding the constitutive presentation of MHC class I immunopeptidomes in primary tissues
Peter Kubiniok,
Ana Marcu,
Leon Bichmann,
Leon Kuchenbecker,
Heiko Schuster,
David J. Hamelin,
Jérôme D. Duquette,
Kevin A. Kovalchik,
Laura Wessling,
Oliver Kohlbacher,
Hans-Georg Rammensee,
Marian C. Neidert,
Isabelle Sirois,
Etienne Caron
Affiliations
Peter Kubiniok
CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
Ana Marcu
Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Baden-Württemberg, Germany; Cluster of Excellence iFIT (EXC 2180), “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, 72076 Tübingen, Baden-Württemberg, Germany
Leon Bichmann
Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Baden-Württemberg, Germany; Applied Bioinformatics, Department of Computer Science, University of Tübingen, 72074 Tübingen, Baden-Württemberg, Germany
Leon Kuchenbecker
Applied Bioinformatics, Department of Computer Science, University of Tübingen, 72074 Tübingen, Baden-Württemberg, Germany
Heiko Schuster
Immatics Biotechnologies GmbH, 72076 Tübingen, Baden-Württemberg, Germany
David J. Hamelin
CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
Jérôme D. Duquette
CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
Kevin A. Kovalchik
CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
Laura Wessling
CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
Oliver Kohlbacher
Applied Bioinformatics, Department of Computer Science, University of Tübingen, 72074 Tübingen, Baden-Württemberg, Germany; Institute for Bioinformatics and Medical Informatics, University of Tübingen, 72076 Tübingen, Baden-Württemberg, Germany; Biomolecular Interactions, Max Planck Institute for Developmental Biology, 72076 Tübingen, Baden-Württemberg, Germany; Cluster of Excellence Machine Learning in the Sciences (EXC 2064), University of Tübingen, 72074 Tübingen, Baden-Württemberg, Germany; Translational Bioinformatics, University Hospital Tübingen, 72076 Tübingen, Baden-Württemberg, Germany
Hans-Georg Rammensee
Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Baden-Württemberg, Germany; Cluster of Excellence iFIT (EXC 2180), “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, 72076 Tübingen, Baden-Württemberg, Germany; DKFZ Partner Site Tübingen, German Cancer Consortium (DKTK), 72076 Tübingen, Baden-Württemberg, Germany
Marian C. Neidert
Clinical Neuroscience Center and Department of Neurosurgery, University Hospital and University of Zürich, 8057&8091 Zürich, Switzerland
Isabelle Sirois
CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
Etienne Caron
CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada; Department of Pathology and Cellular Biology, Faculty of Medicine, Université de Montréal, QC H3T 1J4, Canada; Corresponding author
Summary: Understanding the molecular principles that govern the composition of the MHC-I immunopeptidome across different primary tissues is fundamentally important to predict how T cells respond in different contexts in vivo. Here, we performed a global analysis of the MHC-I immunopeptidome from 29 to 19 primary human and mouse tissues, respectively. First, we observed that different HLA-A, HLA-B, and HLA-C allotypes do not contribute evenly to the global composition of the MHC-I immunopeptidome across multiple human tissues. Second, we found that tissue-specific and housekeeping MHC-I peptides share very distinct properties. Third, we discovered that proteins that are evolutionarily hyperconserved represent the primary source of the MHC-I immunopeptidome at the organism-wide scale. Fourth, we uncovered new components of the antigen processing and presentation network, including the carboxypeptidases CPE, CNDP1/2, and CPVL. Together, this study opens up new avenues toward a system-wide understanding of antigen presentation in vivo across mammalian species.
