Dataset Information

The HLA-Ligand-Atlas. A resource of natural HLA ligands presented on benign tissues

ABSTRACT: The human leukocyte antigen (HLA) complex regulates the adaptive immune response by showcasing the intracellular and extracellular protein content to the immune system. T cells recognize these HLA-presented peptides as self or foreign and can elicit an immune response. In this work, we describe the HLA-Ligand-Atlas, a comprehensive map of HLA-I and HLA-II-presented peptides from 30 benign tissues, 51 HLA-I alleles, and 86 HLA-II alleles. Nearly 50% of HLA ligands have not been previously described. Due to the scarcity of benign human samples, the tissue was extracted from different organs at autopsy from human subjects without any diagnosed malignancy. Furthermore, we were able to identify non-canonical HLA-I peptides on benign tissues, showing that their processing is not unique to cancer. This dataset holds great promise in answering both basic and translational questions in fields such as autoimmunity, organ/tissue transplantation, and cancer immunotherapy.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Hans-Georg Rammensee

PROVIDER: MSV000096271 | MassIVE | Thu Oct 31 16:34:00 GMT 2024

SECONDARY ACCESSION(S): PXD019643

REPOSITORIES: MassIVE

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Publications

HLA Ligand Atlas: a benign reference of HLA-presented peptides to improve T-cell-based cancer immunotherapy.

Marcu Ana A Bichmann Leon L Kuchenbecker Leon L Kowalewski Daniel Johannes DJ Freudenmann Lena Katharina LK Backert Linus L Mühlenbruch Lena L Szolek András A Lübke Maren M Wagner Philipp P Engler Tobias T Matovina Sabine S Wang Jian J Hauri-Hohl Mathias M Martin Roland R Kapolou Konstantina K Walz Juliane Sarah JS Velz Julia J Moch Holger H Regli Luca L Silginer Manuela M Weller Michael M Löffler Markus W MW Erhard Florian F Schlosser Andreas A Kohlbacher Oliver O Stevanović Stefan S Rammensee Hans-Georg HG Neidert Marian Christoph MC

Journal for immunotherapy of cancer 20210401 4

<h4>Background</h4>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, ...[more]

PMID: 33858848

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Project description:Treatment of cancer cells with anti-cancer drugs often fails to achieve complete remission. Yet, such drug treatments may induce alteration in the tumorâs gene expression patterns, including those of Cancer/Testis Antigens (CTA). The degradation products of such antigens can be presented as HLA peptides on the surface of the tumor cells and be developed into anti-cancer immunotherapeutics. For example, the DNA methyl transferase inhibitor, 5-aza-2'-deoxycytidine (Decitabine) has limited anti-tumor efficacy, yet it induces the expression of many genes, including CTAs that are normally silenced in the healthy adult tissues. In this study, the presentation of many new HLA peptides derived from CTAs and induced by Decitabine was demonstrated in three human Glioblastoma cell lines. Such presentation of CTA-derived HLA peptides can be exploited for development of new treatment modalities, combining drug treatment with anti-CTA targeted immunotherapy. The Decitabine-induced HLA peptidomes include many CTAs that are not normally detected in healthy tissues or in cancer cells, unless treated with the drug. In addition, the study included large-scale analyses of the simultaneous effects of Decitabine on the transcriptomes, proteomes and HLA peptidomes of the human Glioblastoma cells. It demonstrates the poor correlations between these three levels of gene expression, both in their total levels and in their response to the drug. The transcriptomes, proteomes and HLA peptidomes of the U-87, T98G and LNT-229 GBM human cell lines were analyzed before and after treatment with Decitabine. Overall, the RNA-Seq transcriptome analyses resulted in the identification of above 26000 transcripts, the proteome analyses identified about 7500 proteins and the HLA class I peptidome analyses resulted in above 25000 identified HLA peptides. Two biological repetitions of the transcriptome, three of the proteome and three of the HLA peptidome were performed with each of the cell lines and treatment, resulting in highly reproducible datasets.