RT Journal Article SR Electronic T1 The HLA Ligand Atlas - A resource of natural HLA ligands presented on benign tissues JF bioRxiv FD Cold Spring Harbor Laboratory SP 778944 DO 10.1101/778944 A1 Ana Marcu A1 Leon Bichmann A1 Leon Kuchenbecker A1 Daniel Johannes Kowalewski A1 Lena Katharina Freudenmann A1 Linus Backert A1 Lena Mühlenbruch A1 András Szolek A1 Maren Lübke A1 Philipp Wagner A1 Tobias Engler A1 Sabine Matovina A1 Jian Wang A1 Mathias Hauri-Hohl A1 Roland Martin A1 Konstantina Kapolou A1 Juliane Sarah Walz A1 Julia Velz A1 Holger Moch A1 Luca Regli A1 Manuela Silginer A1 Michael Weller A1 Markus W. Löffler A1 Florian Erhard A1 Andreas Schlosser A1 Oliver Kohlbacher A1 Stefan Stevanović A1 Hans-Georg Rammensee A1 Marian Christoph Neidert YR 2020 UL http://biorxiv.org/content/early/2020/07/09/778944.abstract AB The human leukocyte antigen (HLA) complex controls adaptive immunity by presenting defined fractions of the intracellular and extracellular protein content to immune cells. Here, we describe the HLA Ligand Atlas, an extensive collection of mostly matched HLA-I and -II ligandomes from 225 benign samples (29 tissues, 21 subjects). The initial release covers 51 HLA-I and 86 HLA-II allotypes presenting 89,853 HLA-I- and 140,861 HLA-II ligands. We observe that the immunopeptidomes differ considerably between tissues and individuals on both source protein and HLA-ligand level. 1,407 HLA-I ligands stem from non-canonical genomic regions. We highlight the importance of comparatively analyzing both benign and malignant tissues to inform tumor association, based on a case study in three glioblastoma patients. The resource provides insights into applied and basic immune-associated questions in the context of cancer immunotherapy, infection, transplantation, allergy, and autoimmunity. It is publicly available at www.hla-ligand-atlas.org.Competing Interest StatementLinus Backert, Daniel Johannes Kowalewski, Maren Lübke are employees of Immatics Biotechnologies GmbH. Linus Backert, Daniel J. Kowalewski, Markus W. Löffler, and Stefan Stevanović are inventors of patents owned by Immatics Biotechnologies GmbH. Markus W. Löffler has acted as a paid consultant in cancer immunology for Boehringer Ingehlheim Pharma GmbH & Co. KG. Hans-Georg Rammensee is shareholder of Immatics Biotechnologies GmbH and Curevac AG.