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

doi:10.1016/j.isci.2022.103768

Understanding the constitutive presentation of MHC class I immunopeptidomes in primary tissues

iScience. 2022 Jan 18;25(2):103768. doi: 10.1016/j.isci.2022.103768. eCollection 2022 Feb 18.

Authors

Peter Kubiniok¹, Ana Marcu^{2

3}, Leon Bichmann^{2

4}, Leon Kuchenbecker⁴, Heiko Schuster⁵, David J Hamelin¹, Jérôme D Duquette¹, Kevin A Kovalchik¹, Laura Wessling¹, Oliver Kohlbacher^{4

6

7

8

9}, Hans-Georg Rammensee^{2

3

10}, Marian C Neidert¹¹, Isabelle Sirois¹, Etienne Caron^{1

12}

Affiliations

¹ CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada.
² Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Baden-Württemberg, Germany.
³ Cluster of Excellence iFIT (EXC 2180), "Image-Guided and Functionally Instructed Tumor Therapies", University of Tübingen, 72076 Tübingen, Baden-Württemberg, Germany.
⁴ Applied Bioinformatics, Department of Computer Science, University of Tübingen, 72074 Tübingen, Baden-Württemberg, Germany.
⁵ Immatics Biotechnologies GmbH, 72076 Tübingen, Baden-Württemberg, Germany.
⁶ Institute for Bioinformatics and Medical Informatics, University of Tübingen, 72076 Tübingen, Baden-Württemberg, Germany.
⁷ Biomolecular Interactions, Max Planck Institute for Developmental Biology, 72076 Tübingen, Baden-Württemberg, Germany.
⁸ Cluster of Excellence Machine Learning in the Sciences (EXC 2064), University of Tübingen, 72074 Tübingen, Baden-Württemberg, Germany.
⁹ Translational Bioinformatics, University Hospital Tübingen, 72076 Tübingen, Baden-Württemberg, Germany.
¹⁰ DKFZ Partner Site Tübingen, German Cancer Consortium (DKTK), 72076 Tübingen, Baden-Württemberg, Germany.
¹¹ Clinical Neuroscience Center and Department of Neurosurgery, University Hospital and University of Zürich, 8057&8091 Zürich, Switzerland.
¹² Department of Pathology and Cellular Biology, Faculty of Medicine, Université de Montréal, QC H3T 1J4, Canada.

Abstract

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.

Keywords: Biological sciences; Biomolecules; Immunology; Peptides.