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Full name: HLA Ligand Atlas
Description: The HLA Ligand Atlas is a comprehensive collection of tissue and HLA allele specific HLA ligands that are naturally presented. The data was generated in standardized mass spectrometry experiments and analyzed using a well defined computational analysis workflow.
Year founded: 2019
Last update: 2021-04-23
Real time : Checking...
Country/Region: Germany

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University/Institution: University of Tübingen
Address: Geschwister-Scholl-Platz, 72074 Tübingen in German state of Baden-Wurttemberg.
Country/Region: Germany
Contact name (PI/Team): hla
Contact email (PI/Helpdesk):


HLA Ligand Atlas: a benign reference of HLA-presented peptides to improve T-cell-based cancer immunotherapy. [PMID: 33858848]
Ana 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

BACKGROUND: 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: 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 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 mononuclear cells (PBMCs), healthy lung tissues and cell lines. In a case study in glioblastoma, we show that potential on-target off-tumor adverse events in immunotherapy can be avoided by comparing tumor immunopeptidomes to the provided multi-tissue reference.
CONCLUSION: Given that T-cell-based immunotherapies, such as CAR-T cells, affinity-enhanced T cell transfer, cancer vaccines and immune checkpoint inhibition, have significant side effects, the HLA Ligand Atlas is the first step toward defining tumor-associated targets with an improved safety profile. The resource provides insights into basic and applied immune-associated questions in the context of cancer immunotherapy, infection, transplantation, allergy and autoimmunity. It is publicly available and can be browsed in an easy-to-use web interface at .

J Immunother Cancer. 2021:9(4) | 20 Citations (from Europe PMC, 2022-07-02)


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Created on: 2022-04-25
Curated by:
Lina Ma [2022-06-01]
sun yongqing [2022-05-14]
sun yongqing [2022-05-13]