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https://www.readbyqxmd.com/read/29316918/in-silico-epitope-mapping-and-experimental-evaluation-of-the-merozoite-adhesive-erythrocytic-binding-protein-maebl-as-a-malaria-vaccine-candidate
#1
Pedro Cravo, Renato B Machado, Juliana A Leite, Taizy Leda, Rossarin Suwanarusk, Najara Bittencourt, Letusa Albrecht, Carla Judice, Stefanie C P Lopes, Marcus V G Lacerda, Marcelo U Ferreira, Irene S Soares, Yun Shan Goh, Daniel Y Bargieri, François Nosten, Bruce Russell, Laurent Rénia, Fabio T M Costa
BACKGROUND: Technical limitations for culturing the human malaria parasite Plasmodium vivax have impaired the discovery of vaccine candidates, challenging the malaria eradication agenda. The immunogenicity of the M2 domain of the Merozoite Adhesive Erythrocytic Binding Protein (MAEBL) antigen cloned from the Plasmodium yoelii murine parasite, has been previously demonstrated. RESULTS: Detailed epitope mapping of MAEBL through immunoinformatics identified several MHCI, MHCII and B cell epitopes throughout the peptide, with several of these lying in the M2 domain and being conserved between P...
January 10, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29285385/mhc-class-ii-associated-stomach-cancer-mutations-correlate-with-lack-of-subsequent-tumor-development
#2
John M Yavorski, George Blanck
The role of tumor cell expression of major histocompatibility class II (MHCII) has been controversial, with evidence indicating that tumor cell expression of MHCII may lead to an anti-tumor immune response and to tumor cell apoptosis and that MHCII has pro-tumorigenic functions. The cancer genome atlas (TCGA) indicates numerous deleterious mutations for the highly specific, MHCII transcriptional activation proteins, RFX5, RFXAP, RFXANK and CIITA. Also, mutations in the non-polymorphic, human leukocyte antigen (HLA)-DRA gene, which encodes the heavy chain for the most prominent human MHCII molecule, HLA-DR, are common...
December 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29281002/an-automated-benchmarking-platform-for-mhc-class-ii-binding-prediction-methods
#3
Massimo Andreatta, Thomas Trolle, Zhen Yan, Jason A Greenbaum, Bjoern Peters, Morten Nielsen
Motivation: Computational methods for the prediction of peptide-MHC binding have become an integral and essential component for candidate selection in experimental T cell epitope discovery studies. The sheer amount of published prediction methods - and often discordant reports on their performance - poses a considerable quandary to the experimentalist who needs to choose the best tool for their research. Results: With the goal to provide an unbiased, transparent evaluation of the state-of-the-art in the field, we created an automated platform to benchmark peptide-MHC class II binding prediction tools...
December 21, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29273672/cd1a-presentation-of-endogenous-antigens-by-group-2-innate-lymphoid-cells
#4
Clare S Hardman, Yi-Ling Chen, Maryam Salimi, Rachael Jarrett, David Johnson, Valtteri J Järvinen, Raymond J Owens, Emmanouela Repapi, David J Cousins, Jillian L Barlow, Andrew N J McKenzie, Graham Ogg
Group 2 innate lymphoid cells (ILC2) are effectors of barrier immunity, with roles in infection, wound healing, and allergy. A proportion of ILC2 express MHCII (major histocompatibility complex II) and are capable of presenting peptide antigens to T cells and amplifying the subsequent adaptive immune response. Recent studies have highlighted the importance of CD1a-reactive T cells in allergy and infection, activated by the presentation of endogenous neolipid antigens and bacterial components. Using a human skin challenge model, we unexpectedly show that human skin-derived ILC2 can express CD1a and are capable of presenting endogenous antigens to T cells...
December 22, 2017: Science Immunology
https://www.readbyqxmd.com/read/29246859/dendritic-cell-subsets
#5
REVIEW
Christophe Macri, Ee Shan Pang, Timothy Patton, Meredith O'Keeffe
Dendritic cells (DC) are professional antigen presenting cells comprisinga variety of subsets, as either resident or migrating cells, in lymphoid and non-lymphoid organs. In the steady state DC continually process and present antigens on MHCI and MHCII, processes that are highly upregulated upon activation. By expressing differential sets of pattern recognition receptors different DC subsets are able to respond to a range of pathogenic and danger stimuli, enabling functional specialisation of the DC. The knowledge of functional specialisation of DC subsets is key to efficient priming of T cells, to the design of effective vaccine adjuvants and to understanding the role of different DC in health and disease...
December 12, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29246319/link-between-mhc-fiber-type-and-restoration-of-dystrophin-expression-and-key-components-of-the-dapc-by-tricyclo-dna-mediated-exon-skipping
#6
Saleh Omairi, Kwan-Leong Hau, Henry Collin-Hooper, Federica Montanaro, Aurelie Goyenvalle, Luis Garcia, Ketan Patel
Exon skipping mediated by tricyclo-DNA (tc-DNA) antisense oligonucleotides has been shown to induce significant levels of dystrophin restoration in mdx, a mouse model of Duchenne muscular dystrophy. This translates into significant improvement in key disease indicators in muscle, cardio-respiratory function, heart, and the CNS. Here we examine the relationship between muscle fiber type, based on myosin heavy chain (MHC) profile, and the ability of tc-DNA to restore not only dystrophin but also other members of the dystrophin-associated glycoprotein complex (DAPC)...
December 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29231862/conserved-binding-regions-provide-the-clue-for-peptide-based-vaccine-development-a-chemical-perspective
#7
REVIEW
Hernando Curtidor, César Reyes, Adriana Bermúdez, Magnolia Vanegas, Yahson Varela, Manuel E Patarroyo
Synthetic peptides have become invaluable biomedical research and medicinal chemistry tools for studying functional roles, i.e., binding or proteolytic activity, naturally-occurring regions' immunogenicity in proteins and developing therapeutic agents and vaccines. Synthetic peptides can mimic protein sites; their structure and function can be easily modulated by specific amino acid replacement. They have major advantages, i.e., they are cheap, easily-produced and chemically stable, lack infectious and secondary adverse reactions and can induce immune responses via T- and B-cell epitopes...
December 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29203869/trpm7-kinase-activity-is-essential-for-t-cell-colonization-and-alloreactivity-in-the-gut
#8
Andrea Romagnani, Valentina Vettore, Tanja Rezzonico-Jost, Sarah Hampe, Elsa Rottoli, Wiebke Nadolni, Michela Perotti, Melanie A Meier, Constanze Hermanns, Sheila Geiger, Gunther Wennemuth, Camilla Recordati, Masayuki Matsushita, Susanne Muehlich, Michele Proietti, Vladimir Chubanov, Thomas Gudermann, Fabio Grassi, Susanna Zierler
The melastatin-like transient-receptor-potential-7 protein (TRPM7), harbouring a cation channel and a serine/threonine kinase, has been implicated in thymopoiesis and cytokine expression. Here we show, by analysing TRPM7 kinase-dead mutant (Trpm7 R/R ) mice, that the enzymatic activity of the receptor is not essential for thymopoiesis, but is required for CD103 transcription and gut-homing of intra-epithelial lymphocytes. Defective T cell gut colonization reduces MHCII expression in intestinal epithelial cells...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29203716/immune-tolerance-therapies-for-autoimmune-diseases-based-on-heat-shock-protein-t-cell-epitopes
#9
REVIEW
Willem van Eden
Experimental models of autoimmune diseases have revealed the disease protective role of heat shock proteins (HSPs). Both the administration of exogenous extracellular, mostly recombinant, HSP and the experimental co-induction of endogenous intracellular HSP in models have been shown to lead to production of disease protective regulatory T cells (Tregs). Similar to HSP taken up from extracellular bodily fluids, due to stress-related autophagy upregulated HSP also from intracellular sources is a major provider for the major histocompatibility class II (MHCII) ligandome; therefore, both extracellular and intracellular HSP can be prominent targets of Treg...
January 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29175593/rational-selection-of-immunodominant-and-preserved-epitope-sm043300e-from-schistosoma-mansoni-and-design-of-a-chimeric-molecule-for-biotechnological-purposes
#10
Cláudia de Souza, Marcelo Donizete Lopes, Flávio Martins De Oliveira, Maria Juliana Ferreira Passos, Laís Cunha Grossi Ferreira, Bruna Franciele Faria, José Augusto Ferreira Perez Villar, Moacyr Comar Junior, Alex Guterres Taranto, Luciana Lara Dos Santos, Cristina Toscano Fonseca, Débora de Oliveira Lopes
Human schistosomiasis is a neglected tropical disease of great importance in public health. A large number of people are infected with schistosomiasis, making vaccine development and effective diagnosis important control strategies. A rational epitope prediction workflow using Schistosoma mansoni hypothetical proteins was previously presented by our group, and an improvement to that approach is presented here. Briefly, immunodominant epitopes from parasite membrane proteins were predicted by reverse vaccinology strategy with additional in silico analysis...
November 22, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29173586/differential-immune-related-gene-expression-in-the-spleens-of-duck-tembusu-virus-infected-goslings
#11
Yu He, Anqi Wang, Shun Chen, Zhen Wu, Jinyue Zhang, Mingshu Wang, Renyong Jia, Dekang Zhu, Mafeng Liu, Qiao Yang, Ying Wu, Kunfeng Sun, Xiaoyue Chen, Anchun Cheng
Flaviviruses pose a significant threat to public health worldwide. Recently, a novel flavivirus, duck Tembusu virus (TMUV), was identified as the causative agent of a serious duck viral disease in Asia. Its rapid spread and expanded host range have raised substantial concerns regarding its potential threat to non-avian hosts, including humans. However, the specific molecular host responses to this virus are poorly understood. In this study, we used the RNA-sequencing technique to analyse the differential gene expression in the spleens of infected goslings 5days post-infection...
December 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/29170668/epitope-specific-tolerance-modes-differentially-specify-susceptibility-to-proteolipid-protein-induced-experimental-autoimmune-encephalomyelitis
#12
Lei Wang, Julia Winnewisser, Christine Federle, Gregor Jessberger, Klaus-Armin Nave, Hauke B Werner, Bruno Kyewski, Ludger Klein, Maria Hinterberger
Immunization with myelin components can elicit experimental autoimmune encephalomyelitis (EAE). EAE susceptibility varies between mouse strains, depending on the antigen employed. BL/6 mice are largely resistant to EAE induction with proteolipid protein (PLP), probably a reflection of antigen-specific tolerance. However, the extent and mechanism(s) of tolerance to PLP remain unclear. Here, we identified three PLP epitopes in PLP-deficient BL/6 mice. PLP-sufficient mice did not respond against two of these, whereas tolerance was "leaky" for an epitope with weak predicted MHCII binding, and only this epitope was encephalitogenic...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29162901/microrna-449a-modulates-medullary-thymic-epithelial-cell-differentiation
#13
Pengfei Chen, Haohao Zhang, Xiaohua Sun, Yiming Hu, Wenxia Jiang, Zhanjie Liu, Sanhong Liu, Xiaoren Zhang
Medullary thymic epithelial cells (mTECs) ectopically express a diversity of peripheral tissue-restricted antigens (PTAs) and provide unique cues for the expansion, maturation and selection of a repertoire of functionally diverse T lymphocytes. Genetic deletion of all mature microRNAs in thymic epithelial cells (TECs) results in premature thymic involution, progressive disorganisation of the thymic epithelium, and alteration in thymic T cell lineage commitment, consequently eliciting autoimmune disorders. In the present study, we identified that microRNA-449a (miR-449a), a member of miR-449 cluster, regulated mTEC differentiation...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29162163/%C3%AE-synuclein-fibrils-recruit-peripheral-immune-cells-in-the-rat-brain-prior-to-neurodegeneration
#14
Ashley S Harms, Vedad Delic, Aaron D Thome, Nicole Bryant, Zhiyong Liu, Sidhanth Chandra, Asta Jurkuvenaite, Andrew B West
Genetic variation in a major histocompatibility complex II (MHCII)-encoding gene (HLA-DR) increases risk for Parkinson disease (PD), and the accumulation of MHCII-expressing immune cells in the brain correlates with α-synuclein inclusions. However, the timing of MHCII-cell recruitment with respect to ongoing neurodegeneration, and the types of cells that express MHCII in the PD brain, has been difficult to understand. Recent studies show that the injection of short α-synuclein fibrils into the rat substantia nigra pars compacta (SNpc) induces progressive inclusion formation in SNpc neurons that eventually spread to spiny projection neurons in the striatum...
November 21, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29155051/peripheral-monocyte-entry-is-required-for-alpha-synuclein-induced-inflammation-and-neurodegeneration-in-a-model-of-parkinson-disease
#15
Ashley S Harms, Aaron D Thome, Zhaoqi Yan, Aubrey M Schonhoff, Gregory P Williams, Xinru Li, Yudong Liu, Hongwei Qin, Etty N Benveniste, David G Standaert
Accumulation of alpha-synuclein (α-syn) in the central nervous system (CNS) is a core feature of Parkinson disease (PD) that leads to activation of the innate immune system, production of inflammatory cytokines and chemokines, and subsequent neurodegeneration. Here, we used heterozygous reporter knock-in mice in which the first exons of the fractalkine receptor (CX3CR1) and of the C-C chemokine receptor type 2 (CCR2) are replaced with fluorescent reporters to study the role of resident microglia (CX3CR1+) and infiltrating peripheral monocytes (CCR2+), respectively, in the CNS...
November 16, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29152317/bone-marrow-derived-multipotent-mesenchymal-stromal-cells-from-horses-after-euthanasia
#16
Carmen Schröck, Carina Eydt, Florian Geburek, Lena Kaiser, Felicitas Päbst, Janina Burk, Christiane Pfarrer, Carsten Staszyk
Allogeneic equine multipotent mesenchymal stromal cells (eMSCs) have been proposed for use in regenerative therapies in veterinary medicine. A source of allogeneic eMSCs might be the bone marrow from euthanized horses. The purpose of this study was to compare in vitro characteristics of equine bone marrow derived eMSC (eBM-MSCs) from euthanized horses (eut-MSCs) and from narcotized horses (nar-MSCs). Eut-MSCs and nar-MSCs showed typical eMSC marker profiles (positive: CD44, CD90; negative: CD11a/CD18 and MHCII) and possessed tri-lineage differentiation characteristics...
November 2017: Veterinary Medicine and Science
https://www.readbyqxmd.com/read/29141824/inhibition-of-neurogenesis-in-a-case-of-marburg-variant-multiple-sclerosis
#17
Celia Oreja-Guevara, Ulises Gómez-Pinedo, Julia García-López, Rafael Sánchez-Sánchez, Roberto Valverde-Moyano, Alberto Rabano-Gutierrez, Jordi A Matías-Guiu, Ines González-Suárez, Jorge Matías-Guiu
INTRODUCTION: Neural stem cells (NSC) are located essentially in the subventricular zone (SVZ), subgranular zone (SGZ), and along the central canal of the spinal cord. These cells can proliferate in vitro and differentiate into neurons, oligodendrocytes, and astroglia, thus contributing to repair in multiple sclerosis (MS). We conducted a pathological study to analyse neurogenic response in a patient with Marburg variant MS. METHODS: We present the case of a 27-year-old immunocompetent patient with Marburg variant MS, a fulminant form of the disease...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29129227/t-and-b-cell-activation-profiles-from-cows-with-and-without-johne-s-disease-in-response-to-in-vitro-stimulation-with-mycobacterium-avium-subspecies-paratuberculosis
#18
Meredith C Frie, Kelly R B Sporer, Brian W Kirkpatrick, Paul M Coussens
Johne's disease (JD) is a chronic wasting disease of ruminants caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP). JD is particularly problematic on US dairy farms: estimates show that over 50% of farms are MAP-contaminated and as many as 91% of dairy herds could be infected. Although estimates vary widely, JD may cost the dairy industry between $200 million and $1.5 billion every year. One major obstacle to JD management is that JD is difficult to detect in many animals, in part due to the variable immunity against MAP demonstrated by JD+ cattle...
December 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29107027/in-vitro-immunomodulation-of-splenocytes-from-do11-10-mice-by-the-food-colouring-agent-amaranth
#19
David E Lefebvre, Nikia Ross, Andrea L Kocmarek, Simon Cowell, Shelley Dai, Cunye Qiao, Ivan Curran, Terry Koerner, Genevieve S Bondy, Jason H Fine
The chemical amaranth (AM) is permitted as a colouring agent in a variety of foods. Safety was established based on chronic rodent studies. AM and its metabolite naphthionic acid (NA) can be absorbed through the intestine, exposing circulating immune cells including splenocytes. An AM feeding study in rats demonstrated an increase in blood lymphocytes. Yet, in contrast, AM inhibited the delayed-type hypersensitivity reaction to antigen. DO11.10 mice express a T Cell Receptor specific for ovalbumin323-339 peptide (OVAp) presented by I-A(d) MHCII...
November 3, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29027839/ephb-receptors-mainly-ephb3-contribute-to-the-proper-development-of-cortical-thymic-epithelial-cells
#20
Sara Montero-Herradón, Javier García-Ceca, Agustín G Zapata
EphB and their ligands ephrin-B are an important family of protein tyrosine kinase receptors involved in thymocyte-thymic epithelial cell interactions known to be key for the maturation of both thymic cell components. In the present study, we have analyzed the maturation of cortical thymic epithelium in EphB-deficient thymuses evaluating the relative relevance of EphB2 and EphB3 in the process. Results support a relationship between the epithelial hypocellularity of mutant thymuses and altered development of thymocytes, lower proportions of cycling thymic epithelial cells and increased epithelial cell apoptosis...
October 2, 2017: Organogenesis
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