Reference
Reference TypeLive
TitleHLA Ligand Atlas: a benign reference of HLA-presented peptides to improve T-cell-based cancer immunotherapy.
AuthorsAna Marcu; Leon Bichmann; Leon Kuchenbecker; Daniel Johannes Kowalewski; Lena Katharina Freudenmann; Linus Backert; Lena Mühlenbruch; András Szolek; Maren Lübke; Philipp Wagner; Tobias Engler; Sabine Matovina; Jian Wang; Mathias Hauri-Hohl; Roland Martin; Konstantina Kapolou; Juliane Sarah Walz; Julia Velz; Holger Moch; Luca Regli; Manuela Silginer; Michael Weller; Markus W Löffler; Florian Erhard; Andreas Schlosser; Oliver Kohlbacher; Stefan Stevanović; Hans-Georg Rammensee; Marian Christoph Neidert
AffiliationsDepartment of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany ana@hla-ligand-atlas.org; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tübingen, Tübingen, Germany; Applied Bioinformatics, Department of Computer Science, University of Tübingen, Tübingen, Germany; DKFZ Partner Site Tübingen, German Cancer Consortium (DKTK), Tübingen, Germany; Department of Obstetrics and Gynecology, University Hospital of Tübingen, Tübingen, Germany; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Pediatric Stem Cell Transplantation, University Children's Hospital Zurich, Zurich, Switzerland; Clinical Neuroscience Center and Department of Neurosurgery, University Hospital and University of Zurich, Zurich, Switzerland; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), University Hospital of Tübingen, Tübingen, Germany; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology (IKP) and Robert Bosch Center for Tumor Diseases (RBCT), Stuttgart, Germany; Department of Patholog...
JournalJ Immunother Cancer
Year2021
AbstractBACKGROUND: The human leucocyte antigen (HLA) complex controls adaptive immunity by presenting defined fractions of the intracellular and extracellular protein content to immune cells. Understanding the benign HLA ligand repertoire is a prerequisite to define safe T-cell-based immunotherapies against cancer. Due to the poor availability of benign tissues, if available, normal tissue adjacent to the tumor has been used as a benign surrogate when defining tumor-associated antigens. However, this comparison has proven to be insufficient and even resulted in lethal outcomes. In order to match the tumor immunopeptidome with an equivalent counterpart, we created the HLA Ligand Atlas, the first extensive collection of paired HLA-I and HLA-II immunopeptidomes from 227 benign human tissue samples. This dataset facilitates a balanced comparison between tumor and benign tissues on HLA ligand level. METHODS: The human leucocyte antigen (HLA) complex controls adaptive immunity by presenting defined fractions of the intracellular and extracellular protein content to immune cells. Understanding the benign HLA ligand repertoire is a prerequisite to define safe T-cell-based immunotherapies against cancer. Due to the poor availability of benign tissues, if available, normal tissue adjacent to the tumor has been used as a benign surrogate when defining tumor-associated antigens. However, this comparison has proven to be insufficient and even resulted in lethal outcomes. In order to match the tumor immunopeptidome with an equivalent counterpart, we created the HLA Ligand Atlas, the first extensive collection of paired HLA-I and HLA-II immunopeptidomes from 227 benign human tissue samples. This dataset facilitates a balanced comparison between tumor and benign tissues on HLA ligand level.Human tissue samples were obtained from 16 subjects at autopsy, five thymus samples and two ovary samples originating from living donors. HLA ligands were isolated via immunoaffinity purification and analyzed in over 1200 liquid chromatography mass spectrometry runs. Experimentally and computationally reproducible protocols were employed for data acquisition and processing. RESULTS: The human leucocyte antigen (HLA) complex controls adaptive immunity by presenting defined fractions of the intracellular and extracellular protein content to immune cells. Understanding the benign HLA ligand repertoire is a prerequisite to define safe T-cell-based immunotherapies against cancer. Due to the poor availability of benign tissues, if available, normal tissue adjacent to the tumor has been used as a benign surrogate when defining tumor-associated antigens. However, this comparison has proven to be insufficient and even resulted in lethal outcomes. In order to match the tumor immunopeptidome with an equivalent counterpart, we created the HLA Ligand Atlas, the first extensive collection of paired HLA-I and HLA-II immunopeptidomes from 227 benign human tissue samples. This dataset facilitates a balanced comparison between tumor and benign tissues on HLA ligand level.Human tissue samples were obtained from 16 subjects at autopsy, five thymus samples and two ovary samples originating from living donors. HLA ligands were isolated via immunoaffinity purification and analyzed in over 1200 liquid chromatography mass spectrometry runs. Experimentally and computationally reproducible protocols were employed for data acquisition and processing.The initial release covers 51 HLA-I and 86 HLA-II allotypes presenting 90,428 HLA-I- and 142,625 HLA-II ligands. The HLA allotypes are representative for the world population. We observe that immunopeptidomes differ considerably between tissues and individuals on source protein and HLA-ligand level. Moreover, we discover 1407 HLA-I ligands from non-canonical genomic regions. Such peptides were previously described in tumors, peripheral blood mo...
Curation Last Updated2024-05-22 04:23:36
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Epitopes
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MHC Ligand Assays