Dataset Information

The HLA ligandome landscape of chronic myeloid leukemia delineates novel T-cell epitopes for immunotherapy

ABSTRACT: Anti-leukemia immunity plays an important role for disease control and maintenance of tyrosine kinase inhibitor (TKI)-free remission in chronic myeloid leukemia (CML). Antigen-specific immunotherapy holds promise to strengthen immune control in CML, but requires the identification of CML-associated targets. In this study, we used a mass spectrometry-based approach to identify naturally presented HLA class I- and class II-presented peptides in 20 primary CML samples. Comparative HLA ligandome profiling using a comprehensive dataset of different hematological benign specimen delineated a novel panel of frequently expressed CML-exclusive peptides. These non-mutated target antigens are of particular relevance since our extensive data-mining approach demonstrated absence of naturally presented BCR-ABL- and ABL-BCR-derived HLA-presented peptides and the lack of frequent tumor-exclusive presentation of predescribed cancer/testis and leukemia-associated antigens. Functional characterization revealed spontaneous T-cell responses against the newly identified CML-associated peptides in CML patients and their ability to de novo induce multifunctional and cytotoxic antigen-specific T cells in healthy volunteers and CML patients. This characterizes these antigens as prime candidates for T cell-based immunotherapy approaches that may prolong TKI-free survival and even mediate cure of CML patients.

INSTRUMENT(S): LTQ Orbitrap XL

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Peripheral Blood Mononuclear Cell

DISEASE(S): Chronic Myeloid Leukemia

SUBMITTER: Annika Nelde

LAB HEAD: Juliane S. Walz

PROVIDER: PXD010450 | Pride | 2018-12-11

REPOSITORIES: Pride

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The HLA ligandome landscape of chronic myeloid leukemia delineates novel T-cell epitopes for immunotherapy.

Bilich Tatjana T Nelde Annika A Bichmann Leon L Roerden Malte M Salih Helmut R HR Kowalewski Daniel J DJ Schuster Heiko H Tsou Chih-Chiang CC Marcu Ana A Neidert Marian C MC Lübke Maren M Rieth Jonas J Schemionek Mirle M Brümmendorf Tim H TH Vucinic Vladan V Niederwieser Dietger D Bauer Jens J Märklin Melanie M Peper Janet K JK Klein Reinhild R Kohlbacher Oliver O Kanz Lothar L Rammensee Hans-Georg HG Stevanović Stefan S Walz Juliane S JS

Blood 20181210 6

Antileukemia immunity plays an important role in disease control and maintenance of tyrosine kinase inhibitor (TKI)-free remission in chronic myeloid leukemia (CML). Thus, antigen-specific immunotherapy holds promise for strengthening immune control in CML but requires the identification of CML-associated targets. In this study, we used a mass spectrometry-based approach to identify naturally presented HLA class I- and class II-restricted peptides in primary CML samples. Comparative HLA ligandom ...[more]

PMID: 30530751

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Project description:Biomaterials play an increasing role in clinical applications and regenerative medicine. Modern biomaterials should imitate the function of damaged tissue without triggering an immune response, initiate self-regeneration of the body and gradually degrade after implantation. The immune system is now well recognized to play a major role in influencing the biocompatibility of implanted medical devices. To develop a better understanding of the effects of biomaterials on the immune response, we have developed a highly sensitive novel test system capable of examining changes in the immune system by biomaterial. Here, we evaluate for the first time the immunopeptidome, a highly sensitive system that reflects cancer transformation, virus or drug influences and passes these changes directly to T cells, as a test system to examine the effects of contact with materials. Since monocytes are one of the first immune cells reacting to biomaterials, we have tested the influence of different materials - stainless steel, aluminum, zinc, high-density polyethylene, polyurethane films containing zinc diethyldithiocarbamate, copper, and zinc sulphate - on the monocytic THP-1 cell line. Material-associated peptides were identified after stimulation with all material types examined. The magnitude of induced changes in the immunopeptidome after the stimulation appears comparable to that of bacterial lipopolysaccharides (LPS). The source proteins of many detected peptides are associated with cytotoxicity, fibrosis, autoimmunity, inflammation and cellular stress. Considering all tested materials, it was found that the LPS-induced cytotoxicity-, inflammation- and cellular stress-associated HLA class I peptides were mainly induced by aluminum and HLA class II peptides mainly by stainless steel. These findings provide some of the first insights into the effects on the immunopeptidome by biomaterials. A more thorough understanding of these effects may enable the design of more biocompatible implant materials using in vitro models in future. This may be achieved through developing a deeper understanding of possible immune responses induced by biomaterials such as fibrosis, inflammation, cytotoxicity, and autoimmune reactions.

Dataset Information

The HLA ligandome landscape of chronic myeloid leukemia delineates novel T-cell epitopes for immunotherapy

Publications

The HLA ligandome landscape of chronic myeloid leukemia delineates novel T-cell epitopes for immunotherapy.

Similar Datasets

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