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Cross-presentation

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https://www.readbyqxmd.com/read/28228336/evaluation-of-hydrophobic-chitosan-based-particulate-formulations-of-porcine-reproductive-and-respiratory-syndrome-virus-vaccine-candidate-t-cell-antigens
#1
Helen Mokhtar, Lucia Biffar, Satyanarayana Somavarapu, Jean-Pierre Frossard, Sarah McGowan, Miriam Pedrera, Rebecca Strong, Jane C Edwards, Margarita Garcia-Durán, Maria Jose Rodriguez, Graham R Stewart, Falko Steinbach, Simon P Graham
PRRS control is hampered by the inadequacies of existing vaccines to combat the extreme diversity of circulating viruses. Since immune clearance of PRRSV infection may not be dependent on the development of neutralising antibodies and the identification of broadly-neutralising antibody epitopes have proven elusive, we hypothesised that conserved T cell antigens represent potential candidates for development of a novel PRRS vaccine. Previously we had identified the M and NSP5 proteins as well-conserved targets of polyfunctional CD8 and CD4 T cells...
February 3, 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28213733/the-localization-of-a-heterologous-displayed-antigen-in-the-baculovirus-budded-virion-determines-the-type-and-strength-of-induced-adaptive-immune-response
#2
Eugenia Tavarone, Guido Nicolás Molina, Sabrina Amalfi, Andrea Peralta, Paula Molinari, Oscar Taboga
In the search of strategies of presentation of heterologous antigens to elicit humoral or cellular immune responses that modulate and properly potentiate each type of response, researchers have been studying baculovirus (BV) as vaccine vectors with promising results. For some years, several research groups explored different antigen presentation approaches using the BV AcNPV by expressing polypeptides on the surface of budded virions or by de novo synthesis of heterologous antigens by transduction of mammalian cells...
February 17, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28190711/cd8-t-cells-orchestrate-pdc-xcr1-dendritic-cell-spatial-and-functional-cooperativity-to-optimize-priming
#3
Anna Brewitz, Sarah Eickhoff, Sabrina Dähling, Thomas Quast, Sammy Bedoui, Richard A Kroczek, Christian Kurts, Natalio Garbi, Winfried Barchet, Matteo Iannacone, Frederick Klauschen, Waldemar Kolanus, Tsuneyasu Kaisho, Marco Colonna, Ronald N Germain, Wolfgang Kastenmüller
Adaptive cellular immunity is initiated by antigen-specific interactions between T lymphocytes and dendritic cells (DCs). Plasmacytoid DCs (pDCs) support antiviral immunity by linking innate and adaptive immune responses. Here we examined pDC spatiotemporal dynamics during viral infection to uncover when, where, and how they exert their functions. We found that pDCs accumulated at sites of CD8(+) T cell antigen-driven activation in a CCR5-dependent fashion. Furthermore, activated CD8(+) T cells orchestrated the local recruitment of lymph node-resident XCR1 chemokine receptor-expressing DCs via secretion of the XCL1 chemokine...
February 8, 2017: Immunity
https://www.readbyqxmd.com/read/28185916/dna-vaccines-for-prostate-cancer
#4
REVIEW
Christopher D Zahm, Viswa Teja Colluru, Douglas G McNeel
DNA vaccines offer many advantages over other anti-tumor vaccine approaches due to their simplicity, ease of manufacturing, and safety. Results from several clinical trials in patients with cancer have demonstrated that DNA vaccines are safe and can elicit immune responses. However, to date few DNA vaccines have progressed beyond phase I clinical trial evaluation. Studies into the mechanism of action of DNA vaccines in terms of antigen-presenting cell types able to directly present or cross-present DNA-encoded antigens, and the activation of innate immune responses due to DNA itself, have suggested opportunities to increase the immunogenicity of these vaccines...
February 6, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28184299/the-role-of-cdc1s-in-vivo-cd8-t-cell-priming-through-cross-presentation
#5
REVIEW
Derek Theisen, Kenneth Murphy
The cDC1 subset of classical dendritic cells is specialized for priming CD8 T cell responses through the process of cross-presentation. The molecular mechanisms of cross-presentation remain incompletely understood because of limited biochemical analysis of rare cDC1 cells, difficulty in their genetic manipulation, and reliance on in vitro systems based on monocyte- and bone-marrow-derived dendritic cells. This review will discuss cross-presentation from the perspective of studies with monocyte- or bone-marrow-derived dendritic cells while highlighting the need for future work examining cDC1 cells...
2017: F1000Research
https://www.readbyqxmd.com/read/28179428/breaking-confinement-unconventional-peptide-presentation-by-major-histocompatibility-mhc-class-i-allele-hla-a-02-01
#6
Soumya G Remesh, Massimo Andreatta, Ge Ying, Thomas Kaever, Morten Nielsen, Curtis McMurtrey, William Hildebrand, Bjoern Peters, Dirk M Zajonc
Peptide antigen-presentation by Major Histocompatibility Class (MHC) I proteins initiates CD8+ T cell mediated immunity against pathogens and cancers. MHC I molecules typically bind peptides with nine amino acids in length with both ends tucked inside the major A and F binding pocket. It has been known for a while that longer peptides can also bind by either bulging out of the groove in the middle of the peptide or by binding in a zig-zag fashion inside the groove. In a recent study, we identified an alternative binding conformation of naturally occurring peptides from Toxoplasma gondii bound by HLA-A*02:01...
February 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28159899/cross-presentation-of-soluble-and-cell-associated-antigen-by-murine-hepatocytes-is-enhanced-by-collectrin-expression
#7
Joseph S Dolina, Sylvia Cechova, Christine K Rudy, Sun-Sang J Sung, William W Tang, Joey Lee, Young S Hahn, Thu H Le
Cross-presentation is a modular series of intracellular events dictating the internalization and subsequent MHC class I (MHC I) display of extracellular Ags. This process has been defined in dendritic cells and plays a fundamental role in the induction of CD8(+) T cell immunity during viral, intracellular bacterial, and antitumor responses. Herein, acute viral infection of murine liver with adenovirus, a model for intrahepatic cross-presentation, confirms hepatocytes directly contribute to cross-presentation of Ags and priming the pool of naive CD8(+) T cells within the liver microenvironment...
February 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28153097/dendritic-cells-cross-present-immunogenic-lentivector-encoded-antigen-from-transduced-cells-to-prime-functional-t-cell-immunity
#8
Alastair Hotblack, Sara Seshadri, Lei Zhang, Sahar Hamrang-Yousefi, Ronjon Chakraverty, David Escors, Clare L Bennett
Recombinant lentiviral vectors (LVs) are highly effective vaccination vehicles that elicit protective T cell immunity in disease models. Dendritic cells (DCs) acquire antigen at sites of vaccination and migrate to draining lymph nodes, where they prime vaccine-specific T cells. The potency with which LVs activate CD8(+) T cell immunity has been attributed to the transduction of DCs at the immunization site and durable presentation of LV-encoded antigens. However, it is not known how LV-encoded antigens continue to be presented to T cells once directly transduced DCs have turned over...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28137885/cgas-is-essential-for-the-antitumor-effect-of-immune-checkpoint-blockade
#9
Hua Wang, Shuiqing Hu, Xiang Chen, Heping Shi, Chuo Chen, Lijun Sun, Zhijian J Chen
cGMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates innate immune responses. cGAS catalyzes the synthesis of cGAMP, which functions as a second messenger that binds and activates the adaptor protein STING to induce type I interferons (IFNs) and other immune modulatory molecules. Here we show that cGAS is indispensable for the antitumor effect of immune checkpoint blockade in mice. Wild-type, but not cGAS-deficient, mice exhibited slower growth of B16 melanomas in response to a PD-L1 antibody treatment...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28125356/the-biology-and-underlying-mechanisms-of-cross-presentation-of-exogenous-antigens-on-mhc-i-molecules
#10
Friedrich M Cruz, Jeff D Colbert, Elena Merino, Barry A Kriegsman, Kenneth L Rock
To monitor the health of cells, the immune system tasks antigen-presenting cells with gathering antigens from other cells and bringing them to CD8 T cells in the form of peptides bound to MHC-I molecules. Most cells would be unable to perform this function because they use their MHC-I molecules to exclusively present peptides derived from the cell's own proteins. However, the immune system evolved mechanisms for dendritic cells and some other phagocytes to sample and present antigens from the extracellular milieu on MHC-I through a process called cross-presentation...
January 11, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28107662/a-simple-and-powerful-co-delivery-system-based-on-ph-responsive-metal-organic-frameworks-for-enhanced-cancer-immunotherapy
#11
Fei Duan, Xiaochen Feng, Xinjian Yang, Wentong Sun, Yi Jin, Huifang Liu, Kun Ge, Zhenhua Li, Jinchao Zhang
Tumor-associated antigens (TAAs)-loaded nanoparticles are able to be actively internalized by antigen-presenting cells (APCs) and have shown promising potential in cancer immunotherapy. However, current TAAs delivery strategy exhibits limitations of complicated synthesis process, low loading efficiency and inefficient CD8(+) cytotoxic T lymphocyte activation leading to unsatisfactory therapeutic effect. Thus, the construction of novel TAAs-delivery systems for enhanced cancer therapy is highly desirable. In this work, we fabricated a very simple yet powerful antigens-delivery system for cancer immunotherapy based-on pH-responsive metal-organic frameworks (MOFs) with size about 30 nm...
January 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28106145/cd1-and-cd1-porcine-blood-dendritic-cells-are-enriched-for-the-orthologues-of-the-two-major-mammalian-conventional-subsets
#12
Jane C Edwards, Helen E Everett, Miriam Pedrera, Helen Mokhtar, Emanuele Marchi, Ferran Soldevila, Daryan A Kaveh, Philip J Hogarth, Helen L Johns, Javier Nunez-Garcia, Falko Steinbach, Helen R Crooke, Simon P Graham
Conventional dendritic cells (cDC) are professional antigen-presenting cells that induce immune activation or tolerance. Two functionally specialised populations, termed cDC1 and cDC2, have been described in humans, mice, ruminants and recently in pigs. Pigs are an important biomedical model species and a key source of animal protein; therefore further understanding of their immune system will help underpin the development of disease prevention strategies. To characterise cDC populations in porcine blood, DC were enriched from PBMC by CD14 depletion and CD172a enrichment then stained with lineage mAbs (Lin; CD3, CD8α, CD14 and CD21) and mAbs specific for CD172a, CD1 and CD4...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102523/the-effect-of-superparamagnetic-iron-oxide-nanoparticle-surface-charge-on-antigen-cross-presentation
#13
Yongbin Mou, Yun Xing, Hongyan Ren, Zhihua Cui, Yu Zhang, Guangjie Yu, Walter J Urba, Qingang Hu, Hongming Hu
Magnetic nanoparticles (NPs) of superparamagnetic iron oxide (SPIO) have been explored for different kinds of applications in biomedicine, mechanics, and information. Here, we explored the synthetic SPIO NPs as an adjuvant on antigen cross-presentation ability by enhancing the intracellular delivery of antigens into antigen presenting cells (APCs). Particles with different chemical modifications and surface charges were used to study the mechanism of action of antigen delivery. Specifically, two types of magnetic NPs, γFe2O3/APTS (3-aminopropyltrimethoxysilane) NPs and γFe2O3/DMSA (meso-2, 3-Dimercaptosuccinic acid) NPs, with the same crystal structure, magnetic properties, and size distribution were prepared...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28090699/modelling-irf8-deficient-human-hematopoiesis-and-dendritic-cell-development-with-engineered-ips-cells
#14
Stephanie Sontag, Malrun Förster, Jie Qin, Paul Wanek, Saskia Mitzka, Herdit M Schüler, Steffen Koschmieder, Stefan Rose-John, Kristin Seré, Martin Zenke
Human induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers, including hematopoietic stem cells and their progeny. Interferon regulatory factor 8 (IRF8) is a transcription factor, which acts in hematopoiesis as lineage determining factor for myeloid cells, including dendritic cells (DC). Autosomal recessive or dominant IRF8 mutations occurring in patients cause severe monocytic and DC immunodeficiency. To study IRF8 in human hematopoiesis we generated human IRF8-/- iPS cells and IRF8-/- embryonic stem (ES) cells using RNA guided CRISPR/Cas9n genome editing...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28090319/the-role-of-liver-sinusoidal-cells-in-local-hepatic-immune-surveillance
#15
REVIEW
Dirk Wohlleber, Percy A Knolle
Although the liver's function as unique immune organ regulating immunity has received a lot of attention over the last years, the mechanisms determining hepatic immune surveillance against infected hepatocytes remain less well defined. Liver sinusoidal cells, in particular, liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs), serve as physical platform for recruitment and anchoring of blood-borne immune cells in the liver. Liver sinusoidal cells also function as portal of entry for infectious microorganisms targeting the liver such as hepatotropic viruses, bacteria or parasites...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28077434/transfer-of-allogeneic-cd4-t-cells-rescues-cd8-t-cells-in-anti-pd-l1-resistant-tumors-leading-to-tumor-eradication
#16
Ainhoa Arina, Theodore Karrison, Eva Galka, Karin Schreiber, Ralph R Weichselbaum, Hans Schreiber
Adoptively transferred CD8(+) T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T-cell-mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule K(b) needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8(+) T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months...
February 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28077213/inhibition-of-dopamine-receptor-d3-signaling-in-dendritic-cells-increases-antigen-cross-presentation-to-cd8-t-cells-favoring-anti-tumor-immunity
#17
Claudio Figueroa, Felipe Gálvez-Cancino, Cesar Oyarce, Francisco Contreras, Carolina Prado, Catalina Valeria, Sebastián Cruz, Alvaro Lladser, Rodrigo Pacheco
Dendritic cells (DCs) display the unique ability for cross-presenting antigens to CD8(+) T-cells, promoting their differentiation into cytotoxic T-lymphocytes (CTLs), which play a pivotal role in anti-tumor immunity. Emerging evidence points to dopamine receptor D3 (D3R) as a key regulator of immunity. Accordingly, we studied how D3R regulates DCs function in anti-tumor immunity. The results show that D3R-deficiency in DCs enhanced expansion of CTLs in vivo and induced stronger anti-tumor immunity. Co-culture experiments indicated that D3R-inhibition in DCs potentiated antigen cross-presentation and CTLs activation...
January 2, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28077081/antigen-presenting-capacity-of-murine-splenic-myeloid-cells
#18
Ying-Ying Hey, Benjamin Quah, Helen C O'Neill
BACKGROUND: The spleen is an important site for hematopoiesis. It supports development of myeloid cells from bone marrow-derived precursors entering from blood. Myeloid subsets in spleen are not well characterised although dendritic cell (DC) subsets are clearly defined in terms of phenotype, development and functional role. Recently a novel dendritic-like cell type in spleen named 'L-DC' was distinguished from other known dendritic and myeloid cells by its distinct phenotype and developmental origin...
January 11, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28032353/allergooncology-the-impact-of-allergy-in-oncology-eaaci-position-paper
#19
E Jensen-Jarolim, H J Bax, R Bianchini, M Capron, C Corrigan, M Castells, D Dombrowicz, T R Daniels-Wells, J Fazekas, E Fiebiger, S Gatault, H J Gould, J Janda, D H Josephs, P Karagiannis, F Levi-Schaffer, A Meshcheryakova, D Mechtcheriakova, Y Mekori, F Mungenast, E A Nigro, M L Penichet, F Redegeld, L Saul, J Singer, J F Spicer, A G Siccardi, E Spillner, M C Turner, E Untersmayr, L Vangelista, S N Karagiannis
Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both antitumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments...
December 29, 2016: Allergy
https://www.readbyqxmd.com/read/28025060/liver-sinusoidal-endothelial-cell-cross-priming-is-supported-by-cd4-t-cell-derived-il-2
#20
Michaela Wittlich, Michael Dudek, Jan P Böttcher, Oliver Schanz, Silke Hegenbarth, Tobias Bopp, Edgar Schmitt, Christian Kurts, Christoph Garbers, Stefan Rose John, Percy A Knolle, Dirk Wohlleber
BACKGROUND & AIMS: Liver sinusoidal endothelial cells (LSECs) are prominent liver-resident antigen (cross-)presenting cells. LSEC cross-priming of naïve CD8 T cells does not require CD4 T cell help in contrast to priming by dendritic cells (DC) but leads to the formation of memory T cells that is preceded by transient Granzyme B (GzmB) expression. Here we provide evidence for a so far unrecognized CD4 T helper cell function in LSEC-induced CD8 T cell activation. METHODS: Naïve CD8 T cells and differentiated T helper 1 (Th1) cells were stimulated by antigen-presenting LSEC, and GzmB expression in CD8 T cells was determined by flow cytometry...
December 23, 2016: Journal of Hepatology
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