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https://www.readbyqxmd.com/read/27909647/what-is-direct-allorecognition
#1
REVIEW
Dominic A Boardman, Jacinta Jacob, Lesley A Smyth, Giovanna Lombardi, Robert I Lechler
Direct allorecognition is the process by which donor-derived major histocompatibility complex (MHC)-peptide complexes, typically presented by donor-derived 'passenger' dendritic cells, are recognised directly by recipient T cells. In this review, we discuss the two principle theories which have been proposed to explain why individuals possess a high-precursor frequency of T cells with direct allospecificity and how self-restricted T cells recognise allogeneic MHC-peptide complexes. These theories, both of which are supported by functional and structural data, suggest that T cells recognising allogeneic MHC-peptide complexes focus either on the allopeptides bound to the allo-MHC molecules or the allo-MHC molecules themselves...
2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/27907215/cd8-t-cells-induce-fatal-brainstem-pathology-during-cerebral-malaria-via-luminal-antigen-specific-engagement-of-brain-vasculature
#2
Phillip A Swanson, Geoffrey T Hart, Matthew V Russo, Debasis Nayak, Takele Yazew, Mirna Peña, Shahid M Khan, Chris J Janse, Susan K Pierce, Dorian B McGavern
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection that results in thousands of deaths each year, mostly in African children. The in vivo mechanisms underlying this fatal condition are not entirely understood. Using the animal model of experimental cerebral malaria (ECM), we sought mechanistic insights into the pathogenesis of CM. Fatal disease was associated with alterations in tight junction proteins, vascular breakdown in the meninges / parenchyma, edema, and ultimately neuronal cell death in the brainstem, which is consistent with cerebral herniation as a cause of death...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27907183/activation-of-innate-and-adaptive-immunity-by-a-recombinant-human-cytomegalovirus-strain-expressing-an-nkg2d-ligand
#3
Adriana Tomić, Pavankumar R Varanasi, Mijo Golemac, Suzana Malić, Peggy Riese, Eva M Borst, Eva Mischak-Weissinger, Carlos A Guzmán, Astrid Krmpotić, Stipan Jonjić, Martin Messerle
Development of an effective vaccine against human cytomegalovirus (HCMV) is a need of utmost medical importance. Generally, it is believed that a live attenuated vaccine would best provide protective immunity against this tenacious pathogen. Here, we propose a strategy for an HCMV vaccine that aims at the simultaneous activation of innate and adaptive immune responses. An HCMV strain expressing the host ligand ULBP2 for the NKG2D receptor was found to be susceptible to control by natural killer (NK) cells, and preserved the ability to stimulate HCMV-specific T cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27907087/prenylated-polyphenols-from-clusiaceae-and-calophyllaceae-with-immunomodulatory-activity-on-endothelial-cells
#4
Caroline Rouger, Sylvain Pagie, Séverine Derbré, Anne-Marie Le Ray, Pascal Richomme, Béatrice Charreau
Endothelial cells (ECs) are key players in inflammation and immune responses involved in numerous pathologies. Although attempts were experimentally undertaken to prevent and control EC activation, drug leads and probes still remain necessary. Natural products (NPs) from Clusiaceous and Calophyllaceous plants were previously reported as potential candidates to prevent endothelial dysfunction. The present study aimed to identify more precisely the molecular scaffolds that could limit EC activation. Here, 13 polyphenols belonging to 5 different chemical types of secondary metabolites (i...
2016: PloS One
https://www.readbyqxmd.com/read/27903740/protective-t-cell-responses-featured-by-concordant-recognition-of-middle-east-respiratory-syndrome-coronavirus-derived-cd8-t-cell-epitopes-and-host-mhc
#5
William J Liu, Jiaming Lan, Kefang Liu, Yao Deng, Yanfeng Yao, Shaolian Wu, Hong Chen, Lingling Bao, Haifeng Zhang, Min Zhao, Qihui Wang, Lingxia Han, Yan Chai, Jianxun Qi, Jincun Zhao, Songdong Meng, Chuan Qin, George F Gao, Wenjie Tan
The coordinated recognition of virus-derived T cell epitopes and MHC molecules by T cells plays a pivotal role in cellular immunity-mediated virus clearance. It has been demonstrated that the conformation of MHC class I (MHC I) molecules can be adjusted by the presented peptide, which impacts T cell activation. However, it is still largely unknown whether the conformational shift of MHC I influences the protective effect of virus-specific T cells. In this study, utilizing the Middle East respiratory syndrome coronavirus-infected mouse model, we observed that through the unusual secondary anchor Ile5, a CD8(+) T cell epitope drove the conformational fit of Trp(73) on the α1 helix of murine MHC I H-2K(d) In vitro renaturation and circular dichroism assays indicated that this shift of the structure did not influence the peptide/MHC I binding affinity...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27901642/a-generic-rna-pulsed-dc-based-approach-for-developing-therapeutic-intervention-against-nasopharyngeal-carcinoma
#6
Rajeev K Tyagi, Rajesh Parmar, Naisargee Patel
The recurrent nasopharyngeal carcinoma of head-and-neck cancers pathology showed unique symptoms and clinical characteristics. The complexity of pathology poses challenges for developing therapeutic interventional approaches against nasopharyngeal carcinoma (NPC). The conventional treatment regimens offer limited local control and survival, which, leads to adverse delayed complications. Our study present a generic monocyte derived dendritic cell (MoDC) vaccine strategy for NPC in which RNA is used as a source of tumor-associated antigens (TAAgs)...
November 30, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27898464/donor-derived-exosomes-the-trick-behind-the-semidirect-pathway-of-allorecognition
#7
Adrian E Morelli, William Bracamonte-Baran, William J Burlingham
PURPOSE OF REVIEW: The passenger leukocyte hypothesis predicts that after transplantation, donor antigen-presenting cells (APCs) from the graft present donor MHC molecules to directly alloreactive T cells in lymphoid organs. However, in certain transplantation models, recent evidence contradicts this long-standing concept. New findings demonstrate that host, instead of donor, APCs play a prominent role in allosensitization against donor MHC molecules via the semidirect pathway. A similar mechanism operates in development of T-cell split tolerance to noninherited maternal antigens...
November 24, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27895620/excessive-cytosolic-dna-fragments-as-a-potential-trigger-of-graves-disease-an-encrypted-message-sent-by-animal-models
#8
REVIEW
Yuqian Luo, Aya Yoshihara, Kenzaburo Oda, Yuko Ishido, Koichi Suzuki
Graves' hyperthyroidism is caused by autoantibodies directed against the thyroid-stimulating hormone receptor (TSHR) that mimic the action of TSH. The establishment of Graves' hyperthyroidism in experimental animals has proven to be an important approach to dissect the mechanisms of self-tolerance breakdown that lead to the production of thyroid-stimulating TSHR autoantibodies (TSAbs). "Shimojo's model" was the first successful Graves' animal model, wherein immunization with fibroblasts cells expressing TSHR and a major histocompatibility complex (MHC) class II molecule, but not either alone, induced TSAb production in AKR/N (H-2(k)) mice...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27893789/characterization-of-the-canine-mhc-class-i-dla-88-50101-peptide-binding-motif-as-a-prerequisite-for-canine-t-cell-immunotherapy
#9
Sharon M Barth, Christian M Schreitmüller, Franziska Proehl, Kathrin Oehl, Leonie M Lumpp, Daniel J Kowalewski, Moreno Di Marco, Theo Sturm, Linus Backert, Heiko Schuster, Stefan Stevanović, Hans-Georg Rammensee, Oliver Planz
There are limitations in pre-clinical settings using mice as a basis for clinical development in humans. In cancer, similarities exist between humans and dogs; thus, the dog patient can be a link in the transition from laboratory research on mouse models to clinical trials in humans. Knowledge of the peptides presented on MHC molecules is fundamental for the development of highly specific T cell-based immunotherapies. This information is available for human MHC molecules but is absent for the canine MHC. In the present study, we characterized the binding motif of dog leukocyte antigen (DLA) class I allele DLA-88*50101, using human C1R and K562 transfected cells expressing the DLA-88*50101 heavy chain...
2016: PloS One
https://www.readbyqxmd.com/read/27893611/absence-of-mir-182-augments-cardiac-allograft-survival
#10
Liang Wei, Vandana Kaul, Xiumei Qu, Xiaoxing Xiong, Audrey H Lau, Naoharu Iwai, Olivia M Martinez, Sheri M Krams
BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate the posttranscriptional expression of target genes and are important regulators in immune responses. Previous studies demonstrated that the miRNA, miR-182 was significantly increased during allograft rejection. Further, the transcription factor Forkhead box (FOX) protein 1, (FOXO1) was shown to be a target of miR-182. The aim of this study is to further examine the role of miR-182 in alloimmune responses. METHODS: Transplantation of BALB/c cardiac allografts was performed in C57BL/6, miR-182, B6...
November 23, 2016: Transplantation
https://www.readbyqxmd.com/read/27893426/sublethal-exposure-to-alpha-radiation-223ra-dichloride-enhances-various-carcinomas-sensitivity-to-lysis-by-antigen-specific-cytotoxic-t-lymphocytes-through-calreticulin-mediated-immunogenic-modulation
#11
Anthony S Malamas, Sofia R Gameiro, Karin M Knudson, James W Hodge
Radium-223 dichloride (Xofigo®; 223Ra) is an alpha-emitting radiopharmaceutical FDA-approved for the treatment of bone metastases in patients with advanced castration-resistant prostate cancer. It is also being examined clinically in patients with breast and lung carcinoma and patients with multiple myeloma. As with other forms of radiation, the aim of 223Ra is to reduce tumor burden by directly killing tumor cells. External beam (photon) and proton radiation have been shown to augment tumor sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes (CTLs)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27891500/interspecies-communication-between-pathogens-and-immune-cells-via-bacterial-membrane-vesicles
#12
Katerina S Jurkoshek, Ying Wang, Jaffre J Athman, Marian R Barton, Pamela A Wearsch
The production of extracellular vesicles is a universal mechanism for intercellular communication that is conserved across kingdoms. Prokaryotes secrete 50-250 nm membrane vesicles (MVs) in a manner that is regulated by environmental stress and is thought to promote survival. Since many types of host-derived stress are encountered during infection, this implies an important role for MV secretion in bacterial pathogenesis. Accordingly, MVs produced by gram-positive and gram-negative pathogens contain toxins, virulence factors, and other molecules that promote survival in the host...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27891241/no-evidence-of-prenatal-diversifying-selection-at-locus-or-supertype-levels-in-the-dog-mhc-class-ii-loci
#13
Alina K Niskanen, Lorna J Kennedy, Hannes Lohi, Jouni Aspi, Tanja Pyhäjärvi
BACKGROUND: Despite decades of studying, the mechanisms maintaining high diversity in the genes of the Major Histocompatibility Complex (MHC) are still puzzling scientists. In addition to pathogen recognition and other functions, MHC molecules may act prenatally in mate choice and in maternal-foetal interactions. These interactions are potential selective mechanisms that increase genetic diversity in the MHC. During pregnancy, immune response has a dual role: the foetus represents foreign tissue compared to mother, but histo-incompatibility is required for successful pregnancy...
2016: Canine Genetics and Epidemiology
https://www.readbyqxmd.com/read/27891225/unraveling-the-role-of-preexisting-immunity-in-prostate-cancer-patients-vaccinated-with-a-her-2-neu-hybrid-peptide
#14
Ioannis F Voutsas, Eleftheria A Anastasopoulou, Panagiotis Tzonis, Michael Papamichail, Sonia A Perez, Constantin N Baxevanis
BACKGROUND: Cancer vaccines aim at eliciting not only an immune response against specific tumor antigens, but also at enhancing a preexisting immunity against the tumor. In this context, we recently reported on the levels of preexisting immunity in prostate cancer patients vaccinated with the HER-2 hybrid peptide (AE37), during a phase I clinical trial. The purpose of the current study was to correlate between preexisting immunity to the native HER-2 peptide, AE36, and expression of HLA-A2 and -A24 molecules with the clinical outcome...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27874963/study-on-the-functions-and-mechanism-of-immune-functions-of-human-telomerase-reverse-transcriptase-regulating-dendritic-cells-treating-sepsis
#15
H-M Chen, L-Q Wang, H-P Wan, H-Z Wei, L-C Ke, C-Y Liu, Q-Y Tan
OBJECTIVE: We analyzed the functions and mechanisms of immune functions of human telomerase reverse transcriptase regulating dendritic cells (DC) treating sepsis of mice models. MATERIALS AND METHODS: Eighty clean grade Balb/c animals aged from 6 to 8 weeks, weighted from 18 g to 22 g were selected for this study. The DC cells were harvested from the animals and cultivated to transfect with the recombinant eukaryotic expression plasmid hTERT-IRES2-EGFP construct...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27874054/combinational-immunotherapy-with-allo-dribble-vaccines-and-anti-ox40-co-stimulation-leads-to-generation-of-cross-reactive-effector-t-cells-and-tumor-regression
#16
Guangjie Yu, Yuhuan Li, Zhihua Cui, Nicholas P Morris, Andrew D Weinberg, Bernard A Fox, Walter J Urba, Lixin Wang, Hong-Ming Hu
It is well-known that vaccines comprising of irradiated whole tumor cells or tumor-derived heat shock proteins can generate tumor-specific immune responses. In contrast, we showed recently that vaccines composed of autophagosomes (DRibbles) derived from syngeneic sarcomas could induce cross-reactive T-cell responses and cross-protection against the tumor. This unusual property of DRibbles was related to the selective recruitment of defective ribosomal products (DRiPs) and other short-lived proteins (SLiPs) into autophagosomes via sequestosome (SQSTM1, p62) mediated association of ubiquitinated SLiPs to the autophagy gene product LC3...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872213/autocrine-type-i-ifn-signaling-in-dendritic-cells-stimulated-with-fungal-%C3%AE-glucans-or-lipopolysaccharide-promotes-cd8-t-cell-activation
#17
Nargess Hassanzadeh-Kiabi, Alberto Yáñez, Ivy Dang, Gislâine A Martins, David M Underhill, Helen S Goodridge
Type I IFNs are key mediators of immune defense against viruses and bacteria. Type I IFNs were also previously implicated in protection against fungal infection, but their roles in antifungal immunity have not been thoroughly investigated. A recent study demonstrated that bacterial and fungal β-glucans stimulate IFN-β production by dendritic cells (DCs) following detection by the Dectin-1 receptor, but the effects of β-glucan-induced type I IFNs have not been defined. We investigated whether type I IFNs regulate CD8 T cell activation by fungal β-glucan particle-stimulated DCs...
November 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27869818/tcr%C3%AE-tcr%C3%AE-pairing-controls-recognition-of-cd1d-and-directs-the-development-of-adipose-nkt-cells
#18
Joshua A Vieth, Joy Das, Fanomezana M Ranaivoson, Davide Comoletti, Lisa K Denzin, Derek B Sant'Angelo
The interaction between the T cell antigen receptor (TCR) expressed by natural killer T cells (NKT cells) and the antigen-presenting molecule CD1d is distinct from interactions between the TCR and major histocompatibility complex (MHC). Our molecular modeling suggested that a hydrophobic patch created after TCRα-TCRβ pairing has a role in maintaining the conformation of the NKT cell TCR. Disruption of this patch ablated recognition of CD1d by the NKT cell TCR but not interactions of the TCR with MHC. Partial disruption of the patch, while permissive to the recognition of CD1d, significantly altered NKT cell development, which resulted in the selective accumulation of adipose-tissue-resident NKT cells...
November 21, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27863400/differentiated-regulation-of-immune-response-related-genes-between-luad-and-lusc-subtypes-of-lung-cancers
#19
Mengzhu Chen, Xiuying Liu, Jie Du, Xiu-Jie Wang, Lixin Xia
Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the two major subtypes of lung cancer, with LUSC exhibits faster progression rate than LUAD. To investigate the roles of immune-response related genes (IRGs) in lung cancer progression, we used LUAD and LUSC samples at different cancer progression stages, and identified that the expression profiles of IRGs could serve as a better classification marker for cancerous tissues of both LUAD and LUSC. We found that the expression changes of IRGs were different between LUAD and LUSC...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27863161/hla-dr-polymorphisms-influence-in-vivo-responses-to-staphylococcal-toxic-shock-syndrome-toxin-1-in-a-transgenic-mouse-model
#20
A Krogman, A Tilahun, C S David, V R Chowdhary, M P Alexander, G Rajagopalan
Toxic shock syndrome toxin-1 (TSST-1) is a potent superantigen produced by Staphylococcus aureus. In addition to menstrual and nonmenstrual toxic shock syndromes, TSST-1 is also implicated in the immunopathogenesis of pneumonia, infective endocarditis, neonatal exanthematous disease, and atopic dermatitis among others. Superantigens first bind to major histocompatibility complex (MHC) class II molecules and then activate a large proportion of T cells by cross-linking their T cell receptor. As binding to MHC class II molecules is a critical step in the robust activation of the immune system by TSST-1 and other superantigens, polymorphic variations between different HLA-DR alleles could potentially influence the magnitude of immune activation and immunopathology caused by TSST-1...
November 15, 2016: HLA
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