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https://www.readbyqxmd.com/read/28740497/the-role-of-multiscale-protein-dynamics-in-antigen-presentation-and-t-lymphocyte-recognition
#1
R Charlotte Eccleston, Shunzhou Wan, Neil Dalchau, Peter V Coveney
T lymphocytes are stimulated when they recognize short peptides bound to class I proteins of the major histocompatibility complex (MHC) protein, as peptide-MHC complexes. Due to the diversity in T-cell receptor (TCR) molecules together with both the peptides and MHC proteins they bind to, it has been difficult to design vaccines and treatments based on these interactions. Machine learning has made some progress in trying to predict the immunogenicity of peptide sequences in the context of specific MHC class I alleles but, as such approaches cannot integrate temporal information and lack explanatory power, their scope will always be limited...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28738674/complex-consisting-of-%C3%AE-glucan-and-antigenic-peptides-with-cleavage-site-for-glutathione-and-aminopeptidases-induces-potent-cytotoxic-t-lymphocytes
#2
Shinichi Mochizuki, Hiromi Morishita, Kazuo Sakurai
The efficient induction of antigen-specific immune responses requires not only promotion of the uptake of antigens and adjuvant molecules into antigen-presenting cells, but also control of their intracellular behavior. We previously demonstrated that the β-glucan schizophyllan (SPG) can form complexes with CpG oligonucleotides with attached dA40 (CpG-dA/SPG), which can accumulate in macrophages in the draining inguinal lymph nodes and induce strong immune responses. In this study, we prepared various conjugates comprising antigenic peptide (OVA257-264) and dA40, and made complexes with SPG...
July 24, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28733878/role-of-tgf-%C3%AE-in-self-peptide-regulation-of-autoimmunity
#3
REVIEW
Bhagirath Singh, Michael D Krawetz, Rachel M De Lima, Rinee Mukherjee, Pratibha Chaturvedi, Edwin Lee-Chan, Edward H Leiter, Kelly L Summers
Transforming growth factor (TGF)-β has been implicated in regulation of the immune system, including autoimmunity. We have found that TGF-β is readily produced by T cells following immunization with self-peptide epitopes that downregulate autoimmune responses in type 1 diabetes (T1D) prone nonobese diabetic (NOD) mice. These include multiple peptide epitopes derived from the islet β-cell antigens GAD65 (GAD65 p202-221, GAD65 p217-236), GAD67 (GAD67 p210-229, GAD67 p225-244), IGRP (IGRP p123-145, IGRP p195-214) and insulin B-chain (Ins...
July 21, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28732710/cytokine-profiling-in-the-prefrontal-cortex-of-parkinson-s-disease-and-multiple-system-atrophy-patients
#4
Rasmus Rydbirk, Betina Elfving, Mille Dahl Andersen, Mia Aggergaard Langbøl, Jonas Folke, Kristian Winge, Bente Pakkenberg, Tomasz Brudek, Susana Aznar
Parkinson's Disease (PD) and Multiple System Atrophy (MSA) are neurodegenerative diseases characterized neuropathologically by alpha-synuclein accumulation in brain cells. This accumulation is hypothesized to contribute to constitutive neuroinflammation, and to participate in the neurodegeneration. Cytokines, which are the main inflammatory signalling molecules, have been identified in blood and cerebrospinal fluid of PD patients, but studies investigating the human brain levels are scarce. It is documented that neurotrophins, necessary for survival of brain cells and known to interact with cytokines, are altered in the basal ganglia of PD patients...
July 18, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28723951/cd8-t-cells-provide-immune-protection-against-murine-disseminated-endotheliotropic-orientia-tsutsugamushi-infection
#5
Guang Xu, Nicole L Mendell, Yuejin Liang, Thomas R Shelite, Yenny Goez-Rivillas, Lynn Soong, Donald H Bouyer, David H Walker
Scrub typhus, caused by a Gram-negative obligately intracellular coccobacillus, Orientia tsutsugamushi, is a long neglected but important tropical disease. Orientia tsutsugamushi causes illness in one million people each year, and 1 billion people are at risk. Without appropriate diagnosis and treatment, the disease can cause severe multiorgan failure with a case fatality rate of 7-15%. The current gaps in knowledge of immunity include the unknown mechanisms of host immunity to O. tsutsugamushi. Using an intravenous (i...
July 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28720143/mhc-class-ii-expression-and-potential-antigen-presenting-cells-in-the-retina-during-experimental-autoimmune-uveitis
#6
Deborah A Lipski, Rémi Dewispelaere, Vincent Foucart, Laure E Caspers, Matthieu Defrance, Catherine Bruyns, François Willermain
BACKGROUND: Controversy exists regarding which cell types are responsible for autoantigen presentation in the retina during experimental autoimmune uveitis (EAU) development. In this study, we aimed to identify and characterize the retinal resident and infiltrating cells susceptible to express major histocompatibility complex (MHC) class II during EAU. METHODS: EAU was induced in C57BL/6 mice by adoptive transfer of autoreactive lymphocytes from IRBP1-20-immunized animals...
July 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28719653/isolation-of-a-monoclonal-antibody-from-a-phage-display-library-binding-the-rhesus-macaque-mhc-class-i-allomorph-mamu-a1-001
#7
Nathan Holman, Jason T Weinfurter, Trevor R Harsla, Roger W Wiseman, Aaron J Belli, Anthony J Michaels, Keith A Reimann, Robert I DeMars, Matthew R Reynolds
Monoclonal antibodies that bind to human leukocyte antigen (HLA) are useful tools for HLA-typing, tracking donor-recipient chimerisms after bone marrow transplants, and characterizing specific major histocompatibility complexes (MHC) on cell surfaces. Unfortunately, equivalent reagents are not available for rhesus macaques, which are commonly used animal as models in organ transplant and infectious disease research. To address this deficiency, we isolated an antibody that recognizes the common Indian rhesus macaque MHC class I molecule, Mamu-A1*001...
2017: PloS One
https://www.readbyqxmd.com/read/28719024/the-immunoproteasome-an-old-player-with-a-novel-and-emerging-role-in-alloimmunity
#8
S K Eskandari, M A J Seelen, G Lin, J R Azzi
Modern treatment strategies for the maintenance of allograft acceptance frequently target ubiquitously-expressed pathways, leading to significant side-effects and poor long-term allograft outcomes. Constitutive proteasome inhibitors, which have recently been introduced for the treatment of antibody-mediated rejection, target the ubiquitously-expressed proteasome. To limit off-target effects and serious mechanism-based toxicity, however, these inhibitors are administered intermittently and suboptimally. Immunoproteasomes, which are an inducible subset of proteasomes enriched in immune cells, replace constitutive proteasomes after cell exposure to proinflammatory cytokines such as interferon-γ...
July 18, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28716903/autophagy-related-protein-vps34-controls-the-homeostasis-and-function-of-antigen-cross-presenting-cd8%C3%AE-dendritic-cells
#9
Vrajesh V Parekh, Sudheer K Pabbisetty, Lan Wu, Eric Sebzda, Jennifer Martinez, Jianhua Zhang, Luc Van Kaer
The class III PI3K Vacuolar protein sorting 34 (Vps34) plays a role in both canonical and noncanonical autophagy, key processes that control the presentation of antigens by dendritic cells (DCs) to naive T lymphocytes. We generated DC-specific Vps34-deficient mice to assess the contribution of Vps34 to DC functions. We found that DCs from these animals have a partially activated phenotype, spontaneously produce cytokines, and exhibit enhanced activity of the classic MHC class I and class II antigen-presentation pathways...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716484/the-anti-tumor-activity-of-the-stat3-inhibitor-stx-0119-occurs-via-promotion-of-tumor-infiltrating-lymphocyte-accumulation-in-temozolomide-resistant-glioblastoma-cell-line
#10
Yasuto Akiyama, Chizu Nonomura, Tadashi Ashizawa, Akira Iizuka, Ryota Kondou, Haruo Miyata, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Akira Asai, Mamoru Ito, Yoshio Kiyohara, Ken Yamaguchi
STAT3 is considered to be a key molecule to mediating tumor-induced immunosuppression in various manners at tumor sites, by acting through immune-regulatory cytokines derived from the tumor cells. Specific anti-STAT3 inhibitors have been developed using nude mouse models transplanted with human tumor cells. However, mouse systems cannot accurately represent the human immune response induced by STAT3 inhibitors, and more humanized therapeutic model based on human immune cells and tumors are needed. In the present study, an immune-deficient NOG mouse with the deletion of both MHC-class I and class II genes, an MHC-double knockout mouse (dKO-NOG), was developed and used to establish humanized immunotherapeutic model...
July 15, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28714192/secreted-tumor-antigens-immune-biomarkers-for-diagnosis-and-therapy
#11
REVIEW
Els N Meeusen, Elgene Lim, Suresh Mathivanan
With the advent of immunotherapies for cancer, there is growing interest in the identification of tumor antigens. Tumor antigens are self-molecules altered through genetic mutations (neoantigens), protein truncation, protein misfolding or abnormal post translational modifications. To induce an immune response, tumor antigens need to be secreted into the tumor environment and presented to the immune system in the draining lymph nodes, resulting in the generation of tumor-specific effector cells and antibodies...
July 17, 2017: Proteomics
https://www.readbyqxmd.com/read/28708886/kir3dl01-upregulation-on-gut-natural-killer-cells-in-response-to-siv-infection-of-kir-and-mhc-class-i-defined-rhesus-macaques
#12
Moritz Ries, Matthew R Reynolds, Ksenia Bashkueva, Kristin Crosno, Saverio Capuano, Trent M Prall, Roger Wiseman, David H O'Connor, Eva G Rakasz, Hajime Uno, Jeffrey D Lifson, David T Evans
Natural killer cells provide an important early defense against viral pathogens and are regulated in part by interactions between highly polymorphic killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their MHC class I ligands on target cells. We previously identified MHC class I ligands for two rhesus macaque KIRs: KIR3DL01 recognizes Mamu-Bw4 molecules and KIR3DL05 recognizes Mamu-A1*002. To determine how these interactions influence NK cell responses, we infected KIR3DL01+ and KIR3DL05+ macaques with and without defined ligands for these receptors with SIVmac239, and monitored NK cell responses in peripheral blood and lymphoid tissues...
July 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28708252/redundant-and-regulatory-roles-for-tlrs-in-leishmania-infection
#13
REVIEW
Prashant Chauhan, Divanshu Shukla, Debprasad Chattopadhyay, Bhaskar Saha
Toll-like receptors (TLRs) are germ-line encoded, non-clonal innate immune receptors, which are often the first receptors to recognize the molecular patterns on pathogens. Therefore, the immune response initiated by TLRs does have far-reaching consequences on the outcome of an infection. As soon as the cell surface TLRs and other receptors recognize a pathogen, the pathogen is phagocytosed. Inclusion of TLRs in the phagosome results in quicker phagosomal maturation and stronger adaptive immune response, as TLRs influence costimulatory molecules expression and determinant selection by MHC class-II and by MHC class-I for cross-presentation...
July 14, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28707669/-planar-molecular-arrangements-aid-the-design-of-mhc-class-ii-binding-peptides
#14
A Cortés, J Coral, C McLachlan, R Benítez, L Pinilla
The coupling between peptides and MHC-II proteins in the human immune system is not well understood. This work presents an evidence-based hypothesis of a guiding intermolecular force present in every human MHC-II protein (HLA-II). Previously, we examined the spatial positions of the fully conserved residues in all HLA-II protein types. In each one, constant planar patterns were revealed. These molecular planes comprise of amino acid groups of the same chemical species (for example, Gly) distributed across the protein structure...
May 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28700752/role-of-a-novel-immune-modulating-ddr2-expressing-population-in-silica-induced-pulmonary-fibrosis
#15
Lindsay T McDonald, Sara D Johnson, Dayvia L Russell, M Rita I Young, Amanda C LaRue
Micro-injuries associated with chronic inhaled particle exposures are linked with activation of the immune response and are thought to contribute to progression of fibrotic disease. In the pulmonary environment, we have previously demonstrated a heterogeneous population of circulating fibroblast precursors (CFPs), which are defined by expression of the pan-leukocyte marker CD45 and the collagen receptor, discoidin domain receptor-2 (DDR2). This population is derived from the hematopoietic stem cell, expresses collagen, and has a fibroblastic morphology in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28699110/immune-selection-during-tumor-checkpoint-inhibition-therapy-paves-way-for-nk-cell-missing-self-recognition
#16
REVIEW
Karl-Johan Malmberg, Ebba Sohlberg, Jodie P Goodridge, Hans-Gustaf Ljunggren
The ability of NK cells to specifically recognize cells lacking expression of self-MHC class I molecules was discovered over 30 years ago. It provided the foundation for the "missing self" hypothesis. Research in the two past decades has contributed to a detailed understanding of the molecular mechanisms that determine the specificity and strength of NK cell-mediated "missing self" responses to tumor cells. However, in light of the recent remarkable breakthroughs in clinical cancer immunotherapy, the cytolytic potential of NK cells still remains largely untapped in clinical settings...
July 11, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28698575/dual-non-contiguous-peptide-occupancy-of-hla-class-i-evoke-antiviral-human-cd8-t-cell-response-and-form-neo-epitopes-with-self-antigens
#17
Ziwei Xiao, Zhiyong Ye, Vikeramjeet Singh Tadwal, Meixin Shen, Ee Chee Ren
Host CD8 T cell response to viral infections involves recognition of 8-10-mer peptides presented by MHC-I molecules. However, proteasomes generate predominantly 2-7-mer peptides, but the role of these peptides is largely unknown. Here, we show that single short peptides of <8-mer from Latent Membrane Protein 2 (LMP2) of Epstein Barr Virus (EBV) can bind HLA-A*11:01 and stimulate CD8(+) cells. Surprisingly, two peptide fragments between 4-7-mer derived from LMP2(340-349) were able to complement each other, forming combination epitopes that can stimulate specific CD8(+) T cell responses...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698014/adenoviral-expressed-recombinant-granulocyte-monocyte-colony-stimulating-factor-gm-csf-enhances-protective-immunity-induced-by-inactivated-newcastle-disease-virus-ndv-vaccine
#18
Xinglong Wang, Xiangwei Wang, Yanqing Jia, Chongyang Wang, Qinqsong Han, Zen H Lu, Zengqi Yang
Although vaccination has been hugely successful in protecting birds against infection by the New castle disease virus (NDV), newly-emerged highly virulent strains have been found to overcome established immune protection and threaten the poultry industry. The need to improve the immunization efficacy is, therefore, urgent. Here, we tested the potential immunostimulatory adjuvant activity of the adenoviral-expressed recombinant chicken granulocyte monocyte colony stimulating factor (rchGM-CSF) in an inactivated Newcastle Disease Virus (NDV) vaccine...
July 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28696158/immunization-with-hiv-1-envelope-t20-encoding-dna-vaccines-elicits-cross-clade-neutralizing-antibody-responses
#19
S Stenler, K E Lundin, L Hansen, S Petkov, N Mozafari, M Isaguliants, P Blomberg, C I E Smith, D M Goldenberg, C-H Chang, K Ljungberg, J Hinkula, B Wahren
BACKGROUND: Genetic immunization is expected to induce the expression of antigens in a native form. The encoded peptide epitopes are presented on endogenous MHC molecules, mimicking antigen presentation during a viral infection. We have explored the potential of enfuvirtide (T20), a short HIV peptide with antiviral properties, to enhance immune response to HIV antigens. To generate an expression vector, the T20 sequence was cloned into a conventional plasmid, the novel minicircle construct, and a replicon plasmid...
July 11, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28695294/the-role-of-mhc-genes-in-contagious-cancer-the-story-of-tasmanian-devils
#20
REVIEW
Alison Caldwell, Hannah V Siddle
The Tasmanian devil, a marsupial species endemic to the island of Tasmania, harbours two contagious cancers, Devil Facial Tumour 1 (DFT1) and Devil Facial Tumour 2 (DFT2). These cancers pass between individuals in the population via the direct transfer of tumour cells, resulting in the growth of large tumours around the face and neck of affected animals. While these cancers are rare, a contagious cancer also exists in dogs and five contagious cancers circulate in bivalves. The ability of tumour cells to emerge and transmit in mammals is surprising as these cells are an allograft and should be rejected due to incompatibility between Major Histocompatibility Complex (MHC) genes...
July 11, 2017: Immunogenetics
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