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Immunopeptidome

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https://www.readbyqxmd.com/read/29104575/-hotspots-of-antigen-presentation-revealed-by-human-leukocyte-antigen-ligandomics-for-neoantigen-prioritization
#1
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
#2
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 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29027230/immunogenic-stress-and-death-of-cancer-cells-contribution-of-antigenicity-vs-adjuvanticity-to-immunosurveillance
#3
REVIEW
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
https://www.readbyqxmd.com/read/28985418/the-systemhc-atlas-project
#4
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
https://www.readbyqxmd.com/read/28935714/profiling-mhc-ii-immunopeptidome-of-blood-stage-malaria-reveals-that-cdc1-control-the-functionality-of-parasite-specific-cd4-t-cells
#5
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
https://www.readbyqxmd.com/read/28860189/the-major-histocompatibility-complex-class-i-immunopeptidome-of-extracellular-vesicles
#6
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
https://www.readbyqxmd.com/read/28755382/tools-to-define-the-melanoma-associated-immunopeptidome
#7
REVIEW
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
https://www.readbyqxmd.com/read/28649880/understanding-type-1-diabetes-through-proteomics
#8
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
https://www.readbyqxmd.com/read/28630054/slc45a2-a-melanoma-antigen-with-high-tumor-selectivity-and-reduced-potential-for-autoimmune-toxicity
#9
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
https://www.readbyqxmd.com/read/28539110/novel-insights-into-the-hla-class-i-immunopeptidome-and-t-cell-immunosurveillance
#10
REVIEW
Cornelis J M Melief, Jan H Kessler
Advances in mass spectrometry have allowed the high-throughput quantitative identification of human leukocyte antigen (HLA) class I ligands, and recent studies have reported on the breadth and diversity of the HLA class I immunopeptidome. These findings have far-reaching implications for immunosurveillance by T cells and translational value for immunotherapy.
May 24, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28410297/identification-of-immunogenic-epitopes-by-ms-ms
#11
REVIEW
Moreno Di Marco, Janet Kerstin Peper, Hans-Georg Rammensee
The interrogation of cell surface-presented immunogenic epitopes is of great importance to differentiate diseased cells in consequence to malignant transformation or viral infections. On the basis of this knowledge, next-generation immunotherapies against cancers, autoimmunity, or infectious diseases can be developed. The identification of altered peptide repertoires of transformed cells renders mass spectrometry-based analysis indispensable. This is evident considering the low correlation of gene or protein expression alterations, respectively, with changes in the peptide repertoire rendering those analyses less informative...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28406322/mass-spectrometry-based-proteomic-exploration-of-the-human-immune-system-focus-on-the-inflammasome-global-protein-secretion-and-t-cells
#12
Tuula A Nyman, Martina B Lorey, Wojciech Cypryk, Sampsa Matikainen
The immune system is our defense system against microbial infections and tissue injury, and understanding how it works in detail is essential for developing drugs for different diseases. Mass spectrometry-based proteomics can provide in-depth information on the molecular mechanisms involved in immune responses. Areas covered: Summarized are the key immunology findings obtained with MS-based proteomics in the past five years, with a focus on inflammasome activation, global protein secretion, mucosal immunology, immunopeptidome and T cells...
May 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28254787/serine-proteases-enhance-immunogenic-antigen-presentation-on-lung-cancer-cells
#13
Haley L Peters, Satyendra C Tripathi, Celine Kerros, Hiroyuki Katayama, Haven R Garber, Lisa S St John, Lorenzo Federico, Ismail M Meraz, Jack A Roth, Boris Sepesi, Mourad Majidi, Kathryn Ruisaard, Karen Clise-Dwyer, Jason Roszik, Don L Gibbons, John V Heymach, Stephen G Swisher, Chantale Bernatchez, Gheath Alatrash, Samir Hanash, Jeffrey J Molldrem
Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these reinvigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3...
April 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28218747/mhc-i-peptides-get-out-of-the-groove-and-enable-a-novel-mechanism-of-hiv-1-escape
#14
Phillip Pymm, Patricia T Illing, Sri H Ramarathinam, Geraldine M O'Connor, Victoria A Hughes, Corinne Hitchen, David A Price, Bosco K Ho, Daniel W McVicar, Andrew G Brooks, Anthony W Purcell, Jamie Rossjohn, Julian P Vivian
Major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity by capturing peptides for presentation to T cells and natural killer (NK) cells. The peptide termini are tethered within the MHC-I antigen-binding groove, but it is unknown whether other presentation modes occur. Here we show that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended sets characterized by a common motif at position 1 (P1) to P2. Structures of HLA-B*57:01 presenting N-terminally extended peptides, including the immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus protrudes from the peptide-binding groove...
April 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28188227/the-human-leukocyte-antigen-hla-b27-peptidome-in-vivo-in-spondyloarthritis-susceptible-hla-b27-transgenic-rats-and-the-effect-of-erap1-deletion
#15
Eilon Barnea, Dganit Melamed Kadosh, Yael Haimovich, Nimman Satumtira, Martha L Dorris, Mylinh T Nguyen, Robert E Hammer, Tri M Tran, Robert A Colbert, Joel D Taurog, Arie Admon
HLA-B27 is a class I major histocompatibility (MHC-I) allele that confers susceptibility to the rheumatic disease ankylosing spondylitis (AS) by an unknown mechanism. ERAP1 is an aminopeptidase that trims peptides in the endoplasmic reticulum for binding to MHC-I molecules. ERAP1 shows genetic epistasis with HLA-B27 in conferring susceptibility to AS. Male HLA-B27 transgenic rats develop arthritis and serve as an animal model of AS, whereas female B27 transgenic rats remain healthy. We used large scale quantitative mass spectrometry to identify over 15,000 unique HLA-B27 peptide ligands, isolated after immunoaffinity purification of the B27 molecules from the spleens of HLA-B27 transgenic rats...
April 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28159928/a-meta-analysis-of-hla-peptidome-composition-in-different-hematological-entities-entity-specific-dividing-lines-and-pan-leukemia-antigens
#16
Linus Backert, Daniel Johannes Kowalewski, Simon Walz, Heiko Schuster, Claudia Berlin, Marian Christoph Neidert, Mirle Schemionek, Tim H Brümmendorf, Vladan Vucinic, Dietger Niederwieser, Lothar Kanz, Helmut Rainer Salih, Oliver Kohlbacher, Katja Weisel, Hans-Georg Rammensee, Stefan Stevanovic, Juliane Sarah Walz
Hematological malignancies (HM) are highly amenable targets for immunotherapeutic intervention and may be effectively treated by antigen-specific T-cell based treatment. Recent studies demonstrate that physiologically occurring anti-cancer T-cell responses in certain HM entities target broadly presented non-mutated epitopes. HLA ligands are thus implied as prime targets for broadly applicable and antigen-specific off-the-shelf compounds. With the aim of assessing the presence of common targets shared among different HM which may enable addressing a larger patient collective we conducted a meta-analysis of 83 mass spectrometry-based HLA peptidome datasets (comprising 40,361 unique peptide identifications) across four major HM (19 AML, 16 CML, 35 CLL, and 13 MM/MCL samples) and investigated similarities and differences within the HLA presented antigenic landscape...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28011936/the-mhc-class-ii-immunopeptidome-of-lymph-nodes-in-health-and-in-chemically-induced-colitis
#17
Tim Fugmann, Adriana Sofron, Danilo Ritz, Franziska Bootz, Dario Neri
We recently described a mass spectrometry-based methodology that enables the confident identification of hundreds of peptides bound to murine MHC class II (MHCII) molecules. In this article, we describe its application to the characterization of MHCII-bound peptides isolated from lymph nodes (LNs) of C57BL/6 mice. More than 1000 peptides could be identified in individual analyses, allowing a direct comparison of the MHCII peptidome in different types of normal LNs or in animals with colitis. The peptide length distribution and consensus sequences in axillary, brachial, inguinal, and mesenteric LNs were virtually identical, and a substantial portion of identified peptides corresponded to proteins found in all LNs...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27869121/direct-identification-of-clinically-relevant-neoepitopes-presented-on-native-human-melanoma-tissue-by-mass-spectrometry
#18
Michal Bassani-Sternberg, Eva Bräunlein, Richard Klar, Thomas Engleitner, Pavel Sinitcyn, Stefan Audehm, Melanie Straub, Julia Weber, Julia Slotta-Huspenina, Katja Specht, Marc E Martignoni, Angelika Werner, Rüdiger Hein, Dirk H Busch, Christian Peschel, Roland Rad, Jürgen Cox, Matthias Mann, Angela M Krackhardt
Although mutations may represent attractive targets for immunotherapy, direct identification of mutated peptide ligands isolated from human leucocyte antigens (HLA) on the surface of native tumour tissue has so far not been successful. Using advanced mass spectrometry (MS) analysis, we survey the melanoma-associated immunopeptidome to a depth of 95,500 patient-presented peptides. We thereby discover a large spectrum of attractive target antigen candidates including cancer testis antigens and phosphopeptides...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27862975/purification-of-soluble-hla-class-i-complexes-from-human-serum-or-plasma-deliver-high-quality-immuno-peptidomes-required-for-biomarker-discovery
#19
Danilo Ritz, Andreas Gloger, Dario Neri, Tim Fugmann
Soluble human leukocyte antigen class I (sHLA)-peptide complexes have been suggested to play a role in the modulation of immune responses and in immune evasion of cancer cells. The set of peptides eluted from sHLA molecules could serve as biomarker for the monitoring of patients with cancer or other conditions. Here, we describe an improved sHLA peptidomics methodology resulting in the identification of 1816 to 2761 unique peptide sequences from triplicate analyses of serum or plasma taken from three healthy donors...
January 2017: Proteomics
https://www.readbyqxmd.com/read/27846572/a-large-fraction-of-hla-class-i-ligands-are-proteasome-generated-spliced-peptides
#20
Juliane Liepe, Fabio Marino, John Sidney, Anita Jeko, Daniel E Bunting, Alessandro Sette, Peter M Kloetzel, Michael P H Stumpf, Albert J R Heck, Michele Mishto
The proteasome generates the epitopes presented on human leukocyte antigen (HLA) class I molecules that elicit CD8(+) T cell responses. Reports of proteasome-generated spliced epitopes exist, but they have been regarded as rare events. Here, however, we show that the proteasome-generated spliced peptide pool accounts for one-third of the entire HLA class I immunopeptidome in terms of diversity and one-fourth in terms of abundance. This pool also represents a unique set of antigens, possessing particular and distinguishing features...
October 21, 2016: Science
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