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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 post-translational modifications (PTMs) might lead to presentation of peptides harboring PTMs...
March 7, 2018: Proteomics
Joel 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
Jens Fritsche, Barbara Rakitsch, Franziska Hoffgaard, Michael Römer, Heiko Schuster, Daniel J Kowalewski, Martin Priemer, Vlatka Stos-Zweifel, Helen Hoerzer, 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 neo-antigens 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 HLA peptides that can be used to define targets for immunotherapy...
March 5, 2018: Proteomics
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
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
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
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
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
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. In this report, we describe 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
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
Chloe Chong, Fabio Marino, Hui-Song 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...
December 14, 2017: Molecular & Cellular Proteomics: MCP
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
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
Norma Bloy, Pauline Garcia, Céline M Laumont, Jonathan M Pitt, Antonella Sistigu, Gautier Stoll, Takahiro Yamazaki, Eric Bonneil, Aitziber Buqué, Juliette Humeau, Jan W Drijfhout, Guillaume Meurice, Steffen Walter, Jens Fritsche, Toni Weinschenk, Hans-Georg Rammensee, Cornelis Melief, Pierre Thibault, Claude Perreault, Jonathan Pol, Laurence Zitvogel, Laura Senovilla, Guido Kroemer
Cancer cells are subjected to constant selection by the immune system, meaning that tumors that become clinically manifest have managed to subvert or hide from immunosurveillance. Immune control can be facilitated by induction of autophagy, as well as by polyploidization of cancer cells. While autophagy causes the release of ATP, a chemotactic signal for myeloid cells, polyploidization can trigger endoplasmic reticulum stress with consequent exposure of the "eat-me" signal calreticulin on the cell surface, thereby facilitating the transfer of tumor antigens into dendritic cells...
November 2017: Immunological Reviews
Wenguang Shao, Patrick G A Pedrioli, Witold Wolski, Cristian Scurtescu, Emanuel Schmid, Juan A Vizcaíno, Mathieu Courcelles, Heiko Schuster, Daniel Kowalewski, Fabio Marino, Cecilia S L Arlehamn, Kerrie Vaughan, Bjoern Peters, Alessandro Sette, Tom H M Ottenhoff, Krista E Meijgaarden, Natalie Nieuwenhuizen, Stefan H E Kaufmann, Ralph Schlapbach, John C Castle, Alexey I Nesvizhskii, Morten Nielsen, Eric W Deutsch, David S Campbell, Robert L Moritz, Roman A Zubarev, Anders Jimmy Ytterberg, Anthony W Purcell, Miguel Marcilla, Alberto Paradela, Qi Wang, Catherine E Costello, Nicola Ternette, Peter A van Veelen, Cécile A C M van Els, Albert J R Heck, Gustavo A de Souza, Ludvig M Sollid, Arie Admon, Stefan Stevanovic, Hans-Georg Rammensee, Pierre Thibault, Claude Perreault, Michal Bassani-Sternberg, Ruedi Aebersold, Etienne Caron
Mass spectrometry (MS)-based immunopeptidomics investigates the repertoire of peptides presented at the cell surface by major histocompatibility complex (MHC) molecules. The broad clinical relevance of MHC-associated peptides, e.g. in precision medicine, provides a strong rationale for the large-scale generation of immunopeptidomic datasets and recent developments in MS-based peptide analysis technologies now support the generation of the required data. Importantly, the availability of diverse immunopeptidomic datasets has resulted in an increasing need to standardize, store and exchange this type of data to enable better collaborations among researchers, to advance the field more efficiently and to establish quality measures required for the meaningful comparison of datasets...
July 29, 2017: Nucleic Acids Research
Marion Draheim, Myriam F Wlodarczyk, Karine Crozat, Jean-Michel Saliou, Tchilabalo Dilezitoko Alayi, Stanislas Tomavo, Ali Hassan, Anna Salvioni, Claudia Demarta-Gatsi, John Sidney, Alessandro Sette, Marc Dalod, Antoine Berry, Olivier Silvie, Nicolas Blanchard
In malaria, CD4 Th1 and T follicular helper (TFH ) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins...
November 2017: EMBO Molecular Medicine
Silvia A Synowsky, Sally L Shirran, Fiona G M Cooke, Antony N Antoniou, Catherine H Botting, Simon J Powis
Extracellular vesicles (EVs) are released by most cell types and have been associated with multiple immunomodulatory functions. MHC class I molecules have crucial roles in antigen presentation and in eliciting immune responses and are known to be incorporated into EVs. However, the MHC class I immunopeptidome of EVs has not been established. Here, using a small-scale immunoisolation of the antigen serotypes HLA-A*02:01 and HLA-B*27:05 expressed on the Epstein-Barr virus-transformed B cell line Jesthom and MS of the eluted peptides from both cells and EVs, we identified 516 peptides that bind either HLA-A*02:01 or HLA-B*27:05...
October 13, 2017: Journal of Biological Chemistry
Eva Bräunlein, Angela M Krackhardt
Immunotherapies have been traditionally applied in malignant melanoma, which represent one of the most immunogenic tumours. Recently, immune checkpoint modulation has shown high therapeutic efficacy and may provide long-term survival in a significant proportion of affected patients. T cells are the major players in tumour rejection and recognize tumour cells predominantly in an MHC-dependent way. The immunopeptidome comprises the peptide repertoire presented by MHC class I and II molecules on the surface of the body's cells including tumour cells...
December 2017: Immunology
Inne Crèvecoeur, Saurabh Vig, Chantal Mathieu, Lut Overbergh
Auto-immunity against pancreatic beta-cells leads to an absolute shortage of the hormone insulin, resulting in hyperglycemia and the onset of type 1 diabetes (T1D). Proteomic approaches have been used to elucidate the mechanisms of beta-cell dysfunction and death. Areas covered: In the present review, we discuss discoveries in the beta-cell proteome that have contributed to better insights in the role of the beta-cell in T1D. Techniques, such as 2D-DIGE and MALDI imaging, together with new approaches for sample preparation, including laser capture microdissection and immunopeptidomics, have resulted in novel mechanistic insights in the pathogenesis of T1D...
July 2017: Expert Review of Proteomics
Jungsun Park, Amjad H Talukder, Seon A Lim, Kwanghee Kim, Ke Pan, Brenda Melendez, Sherille D Bradley, Kyle R Jackson, Jahan S Khalili, Junmei Wang, Caitlin Creasy, Bih-Fang Pan, Scott E Woodman, Chantale Bernatchez, David Hawke, Patrick Hwu, Kyung-Mi Lee, Jason Roszik, Gregory Lizée, Cassian Yee
Cytotoxic T lymphocyte (CTL)-based immunotherapies have had remarkable success at generating objective clinical responses in patients with advanced metastatic melanoma. Although the melanocyte differentiation antigens (MDA) MART-1, PMEL, and tyrosinase were among the first melanoma tumor-associated antigens identified and targeted with immunotherapy, expression within normal melanocytes of the eye and inner ear can elicit serious autoimmune side effects, thus limiting their clinical potential as CTL targets...
June 19, 2017: Cancer Immunology Research
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