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Immunopeptidome

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https://www.readbyqxmd.com/read/29791771/minimal-information-about-an-immuno-peptidomics-experiment-miaipe
#1
Jennie R Lill, Peter A van Veelen, Stefan Tenzer, Arie Admon, Etienne Caron, Josh Elias, Albert J R Heck, Miguel Marcilla, Fabio Marino, Markus Müller, Bjoern Peters, Anthony Purcell, Alessandro Sette, Theo Sturm, Nicola Ternette, Juan Antonio Vizcaíno, Michal Bassani-Sternberg
Minimal Information about an Immuno-Peptidomics Experiment (MIAIPE) is an initiative of the members of the Human Immuno-Peptidome Project (HIPP), an international program organized by the Human Proteome Organization (HUPO). The aim of the MIAIPE guidelines is to deliver technical guidelines representing the minimal information required to sufficiently support the evaluation and interpretation of immunopeptidomics experiments. The MIAIPE document has been designed to report essential information about sample preparation, mass spectrometric measurement and associated mass spectrometry (MS)-related bioinformatics aspects that are unique to immunopeptidomics and may not be covered by the general proteomics MIAPE (Minimal Information About a Proteomics Experiment) guidelines...
May 23, 2018: Proteomics
https://www.readbyqxmd.com/read/29786170/immunopeptidomic-profiling-of-hla-a2-positive-triple-negative-breast-cancer-identifies-potential-immunotherapy-target-antigens
#2
Nicola Ternette, Marloes J M Olde Nordkamp, Julius Muller, Amanda P Anderson, Annalisa Nicastri, Adrian V S Hill, Benedikt M Kessler, Demin Li
The recent development in immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cells in the treatment of cancer has not only demonstrated the potency of utilising T-cell reactivity for cancer therapy, but has also highlighted the need for developing new approaches to discover targets suitable for such novel therapeutics. Here we analysed the immunopeptidomes of 6 HLA-A2-positive triple negative breast cancer (TNBC) samples by nano-ultra performance liquid chromatography tandem mass spectrometry (nUPLC-MS2 )...
May 22, 2018: Proteomics
https://www.readbyqxmd.com/read/29780384/discrimination-between-human-leukocyte-antigen-class-i-bound-and-co-purified-hiv-derived-peptides-in-immunopeptidomics-workflows
#3
Thomas Partridge, Annalisa Nicastri, Anna E Kliszczak, Louis-Marie Yindom, Benedikt M Kessler, Nicola Ternette, Persephone Borrow
Elucidation of novel peptides presented by human leukocyte antigen (HLA) class I alleles by immunopeptidomics constitutes a powerful approach that can inform the rational design of CD8+ T cell inducing vaccines to control infection with pathogens such as human immunodeficiency virus type 1 (HIV-1) or to combat tumors. Recent advances in the sensitivity of liquid chromatography tandem mass spectrometry instrumentation have facilitated the discovery of thousands of natural HLA-restricted peptides in a single measurement...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29774024/quantification-of-hla-dm-dependent-major-histocompatibility-complex-of-class-ii-immunopeptidomes-by-the-peptide-landscape-antigenic-epitope-alignment-utility
#4
Miguel Álvaro-Benito, Eliot Morrison, Esam T Abualrous, Benno Kuropka, Christian Freund
The major histocompatibility complex of class II (MHCII) immunopeptidome represents the repertoire of antigenic peptides with the potential to activate CD4+ T cells. An understanding of how the relative abundance of specific antigenic epitopes affects the outcome of T cell responses is an important aspect of adaptive immunity and offers a venue to more rationally tailor T cell activation in the context of disease. Recent advances in mass spectrometric instrumentation, computational power, labeling strategies, and software analysis have enabled an increasing number of stratified studies on HLA ligandomes, in the context of both basic and translational research...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29678301/molecular-pathways-for-antigenic-peptide-generation-by-er-aminopeptidase-1
#5
Anastasia Mpakali, Zachary Maben, Lawrence J Stern, Efstratios Stratikos
Endoplasmic Reticulum aminopeptidase 1 (ERAP1) is an intracellular enzyme that can generate or destroy potential peptide ligands for MHC class I molecules. ERAP1 activity influences the cell-surface immunopeptidome and epitope immunodominance patterns but in complex and poorly understood manners. Two main distinct pathways have been proposed to account for ERAP1's effects on the nature and quantity of MHCI-bound peptides: i) ERAP1 trims peptides in solution, generating the correct length for binding to MHCI or overtrimming peptides so that they are too short to bind, and ii) ERAP1 trims peptides while they are partially bound onto MHCI in manner that leaves the peptide amino terminus accessible...
April 17, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29658117/mapping-the-tumour-hla-ligandome-by-mass-spectrometry
#6
REVIEW
Lena Katharina Freudenmann, Ana Marcu, Stefan Stevanović
The entirety of HLA-presented peptides is referred to as the HLA ligandome of a cell or tissue, in tumours often termed immunopeptidome. Mapping the tumour immunopeptidome by mass spectrometry (MS) comprehensively views the pathophysiologically relevant antigenic signature of human malignancies. MS is an unbiased approach stringently filtering the candidates to be tested as opposed to epitope prediction algorithms. In the setting of peptide-specific immunotherapies, MS-based strategies significantly diminish the risk of lacking clinical benefit, as they yield highly enriched amounts of truly presented peptides...
April 15, 2018: Immunology
https://www.readbyqxmd.com/read/29557506/the-natural-hla-ligandome-of-glioblastoma-stem-like-cells-antigen-discovery-for-t-cell-based-immunotherapy
#7
Marian Christoph Neidert, Daniel Johannes Kowalewski, Manuela Silginer, Konstantina Kapolou, Linus Backert, Lena Katharina Freudenmann, Janet Kerstin Peper, Ana Marcu, Sophie Shih-Yüng Wang, Juliane Sarah Walz, Fabian Wolpert, Hans-Georg Rammensee, Reinhard Henschler, Katrin Lamszus, Manfred Westphal, Patrick Roth, Luca Regli, Stefan Stevanović, Michael Weller, Günter Eisele
Glioblastoma is the most frequent malignant primary brain tumor. In a hierarchical tumor model, glioblastoma stem-like cells (GSC) play a major role in tumor initiation and maintenance as well as in therapy resistance and recurrence. Thus, targeting this cellular subset may be key to effective immunotherapy. Here, we present a mass spectrometry-based analysis of HLA-presented peptidomes of GSC and glioblastoma patient specimens. Based on the analysis of patient samples (n = 9) and GSC (n = 3), we performed comparative HLA peptidome profiling against a dataset of normal human tissues...
June 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29513933/gaining-insight-into-posttranslationally-modified-hiv-antigens-and-their-underlying-characteristics
#8
Fabio Marino
Mass spectrometry (MS)-based immunopeptidomics has developed as one of the leading methodologies for comprehensive characterization of in vivo presented human leukocyte antigen (HLA)-bound peptides. Unveiling the identity of HLA-bound peptides derived from diseased cells is crucial to gain knowledge on the constitution of efficient disease-specific T cell responses. The HLA-presented peptidome reflects the status of the cellular proteome, hence disease-related aberrations of posttranslational modifications (PTMs) might lead to presentation of peptides harboring PTMs...
March 7, 2018: Proteomics
https://www.readbyqxmd.com/read/29508533/comparison-of-the-mhc-i-immunopeptidome-repertoire-of-b-cell-lymphoblasts-using-two-isolation-methods
#9
Joël Lanoix, Chantal Durette, Mathieu Courcelles, Émilie Cossette, Simon Comtois-Marotte, Marie-Pierre Hardy, Caroline Côté, Claude Perreault, Pierre Thibault
Significant technological advances in both affinity chromatography and mass spectrometry have facilitated the identification of peptides associated with the major histocompatibility complex class I (MHC I) molecules, and enabled a greater understanding of the dynamic nature of the immunopeptidome of normal and neoplastic cells. While the isolation of MHC I-associated peptides (MIPs) typically used mild acid elution (MAE) or immunoprecipitation (IP), limited information currently exists regarding their respective analytical merits...
March 6, 2018: Proteomics
https://www.readbyqxmd.com/read/29505699/translating-immunopeptidomics-to-immunotherapy-decision-making-for-patient-and-personalized-target-selection
#10
Jens Fritsche, Barbara Rakitsch, Franziska Hoffgaard, Michael Römer, Heiko Schuster, Daniel J Kowalewski, Martin Priemer, Vlatka Stos-Zweifel, Helen Hörzer, Arun Satelli, Annika Sonntag, Valentina Goldfinger, Colette Song, Andrea Mahr, Martina Ott, Oliver Schoor, Toni Weinschenk
Immunotherapy is revolutionizing cancer treatment and has shown success in particular for tumors with a high mutational load. These effects have been linked to neoantigens derived from patient-specific mutations. To expand efficacious immunotherapy approaches to the vast majority of tumor types and patient populations carrying only a few mutations and maybe not a single presented neoepitope, it is necessary to expand the target space to non-mutated cancer-associated antigens. Mass spectrometry enables the direct and unbiased discovery and selection of tumor-specific human leukocyte antigen (HLA) peptides that can be used to define targets for immunotherapy...
March 5, 2018: Proteomics
https://www.readbyqxmd.com/read/29493099/t-cell-immunopeptidomes-reveal-cell-subtype-surface-markers-derived-from-intracellular-proteins
#11
Niclas Olsson, Liora M Schultz, Lichao Zhang, Michael S Khodadoust, Rupa Narayan, Debra K Czerwinski, Ronald Levy, Joshua E Elias
Immunopeptidomes promise novel surface markers as ideal immunotherapy targets, but their characterization by mass spectrometry (MS) remains challenging. Until recently, cell numbers exceeding 109 were needed to survey thousands of HLA ligands. Such limited analytical sensitivity has historically constrained the types of clinical specimens that can be evaluated to cell cultures or bulk tissues. Measuring immunopeptidomes from purified cell subpopulations would be preferable for many applications, particularly those evaluating rare, primary hematopoietic cell lineages...
March 1, 2018: Proteomics
https://www.readbyqxmd.com/read/29476514/mass-spectrometry-based-immunopeptidomics-for-the-discovery-of-cancer-neoantigens
#12
Michal Bassani-Sternberg
Recent data indicate that endogenous mutated cancer proteins can be processed and presented as HLA binding peptides, leading to their recognition in vivo as "non-self." Targeting such neoantigens would enable immune cells to distinguish between normal and cancerous cells, avoiding the risk of autoimmunity. So far, discovery of such neoantigens relies mainly on prediction-based interrogation of the "mutanome" using genomic information as input, followed by highly laborious and time-consuming T cell screening assays...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29476501/origins-technological-development-and-applications-of-peptidomics
#13
Michael Schrader
Peptidomics is the comprehensive characterization of peptides from biological sources mainly by HPLC and mass spectrometry. Mass spectrometry allows the detection of a multitude of single peptides in complex mixtures. The term first appeared in full papers in the year 2001, after over 100 years of peptide research with a main focus on one or a few specific peptides. Within the last 15 years, this new field has grown to over 1200 publications. Mass spectrometry techniques, in combination with other analytical methods, were developed for the fast and comprehensive analysis of peptides in proteomics and specifically adjusted to implement peptidomics technologies...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29446062/predicted-mhc-peptide-binding-promiscuity-explains-mhc-class-i-hotspots-of-antigen-presentation-defined-by-mass-spectrometry-eluted-ligand-data
#14
Emma Christine Jappe, Jens Kringelum, Thomas Trolle, Morten Nielsen
Peptides that bind to and are presented by MHC class I and class II molecules collectively make up the immunopeptidome. In the context of vaccine development, an understanding of the immunopeptidome is essential, and much effort has been dedicated to its accurate and cost-effective identification. Current state-of-the-art methods mainly comprise in silico tools for predicting MHC binding, which is strongly correlated with peptide immunogenicity. However, only a small proportion of the peptides that bind to MHC molecules are, in fact, immunogenic, and substantial work has been dedicated to uncovering additional determinants of peptide immunogenicity...
February 15, 2018: Immunology
https://www.readbyqxmd.com/read/29377634/in-immunopeptidomics-we-need-a-sniper-instead-of-a-shotgun
#15
Pouya Faridi, Anthony Wayne Purcell, Nathan Paul Croft
Immunopeptidomics employs the use of mass spectrometry to identify and quantify peptides presented on the surface of cells by major histocompatibility complex (MHC; human leukocyte antigen [HLA], in humans) molecules, an essential component of adaptive immunity. Currently, immunopeptidomics follows the same or similar workflows as the more established field of shotgun proteomics, yet inherent differences between these two fields create significant drawbacks for the former. In this viewpoint, we would like to highlight such technical issues and provide suggestions for novel workflows that would increase peptide sequencing coverage, depth, and confidence, collectively enhancing the capabilities of the field of immunopeptidomics...
January 29, 2018: Proteomics
https://www.readbyqxmd.com/read/29327813/computational-tools-for-the-identification-and-interpretation-of-sequence-motifs-in-immunopeptidomes
#16
REVIEW
Bruno Alvarez, Carolina Barra, Morten Nielsen, Massimo Andreatta
Recent advances in proteomics and mass-spectrometry have widely expanded the detectable peptide repertoire presented by major histocompatibility complex (MHC) molecules on the cell surface, collectively known as the immunopeptidome. Finely characterizing the immunopeptidome brings about important basic insights into the mechanisms of antigen presentation, but can also reveal promising targets for vaccine development and cancer immunotherapy. This report describes a number of practical and efficient approaches to analyze immunopeptidomics data, discussing the identification of meaningful sequence motifs in various scenarios and considering current limitations...
January 12, 2018: Proteomics
https://www.readbyqxmd.com/read/29295645/favorable-immune-signature-in-cll-patients-defined-by-antigen-specific-t-cell-responses-might-prevent-second-skin-cancers
#17
Juliane Sarah Walz, Daniel Johannes Kowalewski, Linus Backert, Annika Nelde, Oliver Kohlbacher, Benjamin Weide, Lothar Kanz, Helmut Rainer Salih, Hans-Georg Rammensee, Stefan Stevanović
The course of chronic lymphocytic leukemia (CLL), inducing an immunosuppressed state that also affects T cells as central components of adaptive immunity, predisposes patients to develop second malignancies with skin cancer being the most common. Recently, we found that prevalence of memory T cells with specificity for CLL-associated antigens defined by mass spectrometry-based immunopeptidome analysis correlated with a significant survival benefit. Here, we analyzed our CLL patient cohort for second skin (pre)malignancies and found a significantly lower incidence of skin cancer in the patients showing immune responses to CLL-associated antigens...
January 3, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29242379/high-throughput-and-sensitive-immunopeptidomics-platform-reveals-profound-interferon%C3%AE-mediated-remodeling-of-the-human-leukocyte-antigen-hla-ligandome
#18
Chloe Chong, Fabio Marino, HuiSong Pak, Julien Racle, Roy T Daniel, Markus Müller, David Gfeller, George Coukos, Michal Bassani-Sternberg
Comprehensive knowledge of the human leukocyte antigen (HLA) class-I and class-II peptides presented to T-cells is crucial for designing innovative therapeutics against cancer and other diseases. However methodologies for their purification for mass-spectrometry analysis have been a major limitation. We designed a novel high-throughput, reproducible and sensitive method for sequential immuno-affinity purification of HLA-I and -II peptides from up to 96 samples in a plate format, suitable for both cell lines and tissues...
March 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29104575/-hotspots-of-antigen-presentation-revealed-by-human-leukocyte-antigen-ligandomics-for-neoantigen-prioritization
#19
Markus Müller, David Gfeller, George Coukos, Michal Bassani-Sternberg
The remarkable clinical efficacy of the immune checkpoint blockade therapies has motivated researchers to discover immunogenic epitopes and exploit them for personalized vaccines. Human leukocyte antigen (HLA)-binding peptides derived from processing and presentation of mutated proteins are one of the leading targets for T-cell recognition of cancer cells. Currently, most studies attempt to identify neoantigens based on predicted affinity to HLA molecules, but the performance of such prediction algorithms is rather poor for rare HLA class I alleles and for HLA class II...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29093164/the-immunopeptidomic-landscape-of-ovarian-carcinomas
#20
Heiko Schuster, Janet K Peper, Hans-Christian Bösmüller, Kevin Röhle, Linus Backert, Tatjana Bilich, Britta Ney, Markus W Löffler, Daniel J Kowalewski, Nico Trautwein, Armin Rabsteyn, Tobias Engler, Sabine Braun, Sebastian P Haen, Juliane S Walz, Barbara Schmid-Horch, Sara Y Brucker, Diethelm Wallwiener, Oliver Kohlbacher, Falko Fend, Hans-Georg Rammensee, Stefan Stevanović, Annette Staebler, Philipp Wagner
Immunotherapies, particularly checkpoint inhibitors, have set off a revolution in cancer therapy by releasing the power of the immune system. However, only little is known about the antigens that are essentially presented on cancer cells, capable of exposing them to immune cells. Large-scale HLA ligandome analysis has enabled us to exhaustively characterize the immunopeptidomic landscape of epithelial ovarian cancers (EOCs). Additional comparative profiling with the immunopeptidome of a variety of benign sources has unveiled a multitude of ovarian cancer antigens (MUC16, MSLN, LGALS1, IDO1, KLK10) to be presented by HLA class I and class II molecules exclusively on ovarian cancer cells...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
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