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"Cross presentation"

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https://www.readbyqxmd.com/read/29676785/sustained-cross-presentation-capacity-of-murine-splenic-dendritic-cell-subsets-in-vivo
#1
Nataschja I Ho, Marcel G M Camps, Edwin F E de Haas, Ferry Ossendorp
An exclusive feature of dendritic cells (DCs) is their ability to cross-present exogenous antigens in MHC class I molecules. We analyzed the fate of protein antigen in antigen presenting cell (APC) subsets after uptake of naturally formed antigen-antibody complexes in vivo. We observed that murine splenic DC subsets were able to present antigen in vivo for at least a week. After ex vivo isolation of four APC subsets, the presence of antigen in the storage compartments was visualized by confocal microscopy. Although all APC subsets stored antigen for many days, their ability and kinetics in antigen presentation was remarkably different...
April 20, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29675543/improved-vaccine-induced-immune-responses-via-a-ros-triggered-nanoparticle-based-antigen-delivery-system
#2
Xiaoyu Liang, Jianwei Duan, Xuanling Li, Xiaowei Zhu, Youlu Chen, Xiaoli Wang, Hongfan Sun, Deling Kong, Chen Li, Jing Yang
Subunit vaccines that are designed based on recombinant antigens or peptides have shown promising potential as viable substitutes for traditional vaccines due to their better safety and specificity. However, the induction of adequate in vivo immune responses with appropriate effectiveness remains a major challenge for vaccine development. More recently, the implementation of a nanoparticle-based antigen delivery system has been considered a promising approach to improve the in vivo efficacy for subunit vaccine development...
April 20, 2018: Nanoscale
https://www.readbyqxmd.com/read/29669333/the-role-of-proteasome-inhibitor-mg132-in-2-4-dinitrofluorobenzene-induced-atopic-dermatitis-in-nc-nga-mice
#3
Kozo Ohkusu-Tsukada, Daiki Ito, Kimimasa Takahashi
BACKGROUND: Although immunosuppressants for therapy of atopic dermatitis (AD) are still being sought, proteasome inhibitors are also potential candidates for the treatment of AD. Proteasome inhibitors exert various effects by blocking proteasomal degradation and help regulate processes such as apoptosis induction via caspase-9, cell cycle progression via cyclins, NF-κB inactivation via IκB, and downregulation of antigen cross-presentation. The cells targeted by proteasome inhibitors are therefore activated cells undergoing proliferation or differentiation, and antigen-presenting cells carrying out protein degradation...
April 18, 2018: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29661776/targeting-the-leukemia-antigen-pr1-with-immunotherapy-for-the-treatment-of-multiple-myeloma
#4
Gheath Alatrash, Alexander A Perakis, Celine Kerros, Haley L Peters, Pariya Sukhumalchandra, Mao Zhang, Haroon Jakher, Madhushree Zope, Rebecca S Patenia, Anna Sergeeva, Shuhua Yi, Ken H Young, Anne V Philips, Amanda C Herrmann, Haven R Garber, Na Qiao, Jinsheng Weng, Lisa S St John, Sijie Lu, Karen Clise-Dwyer, Elizabeth A Mittendorf, Qing Ma, Jeffrey J Molldrem
PURPOSE: PR1 is a human leukocyte antigen (HLA)-A2 nonameric peptide derived from neutrophil elastase (NE) and proteinase 3 (P3). We have previously shown that PR1 is cross-presented by solid tumors, leukemia, and antigen presenting cells, including B cells. We have also shown that cross-presentation of PR1 by solid tumors renders them susceptible to killing by PR1-targeting immunotherapies. Since multiple myeloma (MM) is derived from B cells, we investigated whether MM is also capable of PR1 cross-presentation and subsequently capable of being targeted using PR1 immunotherapies...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29628306/tumor-resident-dendritic-cells-and-macrophages-modulate-the-accumulation-of-tcr-engineered-t-cells-in-melanoma
#5
Alastair Hotblack, Angelika Holler, Alice Piapi, Sophie Ward, Hans J Stauss, Clare L Bennett
Ongoing clinical trials explore T cell receptor (TCR) gene therapy as a treatment option for cancer, but responses in solid tumors are hampered by the immunosuppressive microenvironment. The production of TCR gene-engineered T cells requires full T cell activation in vitro, and it is currently unknown whether in vivo interactions with conventional dendritic cells (cDCs) regulate the accumulation and function of engineered T cells in tumors. Using the B16 melanoma model and the inducible depletion of CD11c+ cells in CD11c...
March 16, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29628230/chitosan-stabilized-nasal-emulsion-delivery-system-for-effective-humoral-and-cellular-response-against-recombinant-tetravalent-dengue-antigen
#6
Sravanthi Vemireddy, Preethi Pallavi M C, Sampath Kumar Halmuthur M
Nasal vaccine delivery systems are emerging alternatives to the conventional sub unit vaccine delivery systems owing to their ability to stimulate potent antigen specific humoral and cellular immune responses. Additional virtue of nasal delivery is its close proximity of immune cells to external epithelial layer which is the route of entry to pathogens. Toxicity of emulsion based vaccine delivery systems may be attributed to the presence of high quantities of surfactants used for stabilizing the emulsions. A safer approach would be to reduce physiologically unwanted surfactant burden in the emulsion to the bare limit to necessity...
June 15, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29618478/nadph-oxidase-activation-regulates-apoptotic-neutrophil-clearance-by-murine-macrophages
#7
Juhi Bagaitkar, Jing Huang, Melody Yue Zeng, Nancy K Pech, Darlene A Monlish, Lizet J Perez-Zapata, Irina Miralda, Laura G Schuettpelz, Mary C Dinauer
The phagocyte NADPH oxidase generates superoxide, the precursor to reactive oxygen species (ROS) that have both antimicrobial and immunoregulatory functions. Inactivating mutations in NADPH oxidase alleles cause chronic granulomatous disease (CGD), characterized by enhanced susceptibility to life-threatening microbial infections and inflammatory disorders, and hypomorphic NADPH oxidase alleles are associated with autoimmunity. Impaired apoptotic cell (AC) clearance is implicated as an important contributing factor in chronic inflammation and autoimmunity, but the role of NADPH oxidase-derived ROS in this process is incompletely understood...
April 4, 2018: Blood
https://www.readbyqxmd.com/read/29595473/topoisomerase-vi-senses-and-exploits-both-dna-crossings-and-bends-to-facilitate-strand-passage
#8
Timothy J Wendorff, James M Berger
Type II topoisomerases manage DNA supercoiling and aid chromosome segregation using a complex, ATP-dependent duplex strand passage mechanism. Type IIB topoisomerases and their homologs support both archaeal/plant viability and meiotic recombination. Topo VI, a prototypical type IIB topoisomerase, comprises two Top6A and two Top6B protomers; how these subunits cooperate to engage two DNA segments and link ATP turnover to DNA transport is poorly understood. Using multiple biochemical approaches, we show that Top6B, which harbors the ATPase activity of topo VI, recognizes and exploits the DNA crossings present in supercoiled DNA to stimulate subunit dimerization by ATP...
March 29, 2018: ELife
https://www.readbyqxmd.com/read/29594331/extracellular-vesicle-mediated-mhc-cross-dressing-in-immune-homeostasis-transplantation-infectious-diseases-and-cancer
#9
REVIEW
Furong Zeng, Adrian E Morelli
Eukaryotic cells employ different types of extracellular vesicles (EVs) to exchange proteins, mRNAs, non-coding regulatory RNAs, carbohydrates, and lipids. Cells of the immune system, in particular antigen (Ag)-presenting cells (APCs), acquire major histocompatibility complex (MHC) class I and II molecules loaded with antigenic peptides from leukocytes and tissue parenchymal and stromal cells, through a mechanism known as MHC cross-dressing. Increasing evidence indicates that cross-dressing of APCs with pre-formed Ag-peptide/MHC complexes (pMHCs) is mediated via passage of clusters of EVs with characteristics of exosomes...
March 28, 2018: Seminars in Immunopathology
https://www.readbyqxmd.com/read/29575556/development-of-a-vaccine-based-on-bacteria-mimicking-tumor-cells-coated-with-novel-engineered-tlr2-ligands
#10
Takashi Akazawa, Toshimitsu Ohashi, Viskam Wijewardana, Kikuya Sugiura, Norimitsu Inoue
For a successful tumor vaccine, it is necessary to develop effective immuno-adjuvants and identify specific tumor antigens. Tumor cells obtained from surgical or biopsy tissues are a good source of tumor antigens but, unlike bacteria, they do not induce strong immune responses. Here, we designed two novel lipopeptides that coat tumor cell surfaces and mimic bacterial components. Tumor cells coated with these lipopeptides (called bacteria-mimicking tumor cells (BMTCs)) were prepared and their efficacy as a tumor vaccine examined...
March 25, 2018: Cancer Science
https://www.readbyqxmd.com/read/29563123/murine-cmv-induces-type-1-ifn-that-impairs-differentiation-of-mdscs-critical-for-transplantation-tolerance
#11
Anil Dangi, Lei Zhang, Xiaomin Zhang, Xunrong Luo
Clinical tolerance without immunosuppression has now been achieved for organ transplantation, and its scope will likely continue to expand. In this context, a previously understudied and now increasingly relevant area is how microbial infections might affect the efficacy of tolerance. A highly prevalent and clinically relevant posttransplant pathogen is cytomegalovirus (CMV). Its impact on transplantation tolerance and graft outcomes is not well defined. Employing a mouse model of CMV (MCMV) infection and allogeneic pancreatic islet transplantation in which donor-specific tolerance was induced by infusing donor splenocytes rendered apoptotic by treatment with ethylenecarbodiimide, we investigated the effect of CMV infection on transplantation tolerance induction...
March 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29559473/erap1-dependent-antigen-cross-presentation-determines-efficacy-of-adoptive-t-cell-therapy-in-mice
#12
Karin Schmidt, Christin Keller, Anja A Kühl, Ana Textor, Ulrike Seifert, Thomas Blankenstein, Gerald Willimsky, Peter-Michael Kloetzel
Cytotoxic T lymphocytes can reject established tumors if their target peptide is efficiently presented by major histocompatibility complex class I molecules (pMHC-I) on the surface of cancerous cells. Therapeutic success upon adoptive T cell transfer (ATT), however, requires additional cross-presentation of the same pMHC-I on non-cancerous cells. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an enzyme that customizes the N-terminus of proteasome-generated peptides so they can be loaded onto MHC-I molecules in the endoplasmic reticulum (ER)...
March 20, 2018: Cancer Research
https://www.readbyqxmd.com/read/29555965/mechanisms-underlying-the-lack-of-endogenous-processing-and-clip-mediated-binding-of-the-invariant-chain-by-hla-dp-84gly
#13
Mark Anczurowski, Yuki Yamashita, Munehide Nakatsugawa, Toshiki Ochi, Yuki Kagoya, Tingxi Guo, Chung-Hsi Wang, Muhammed A Rahman, Kayoko Saso, Marcus O Butler, Naoto Hirano
While the principles of classical antigen presentation via MHC class II are well-established, the mechanisms for the many routes of cross-presentation by which endogenous antigens become associated with class II molecules are not fully understood. We have recently demonstrated that the single amino acid polymorphism HLA-DPβ84Gly (DP84Gly ) is critical to abrogate class II invariant chain associated peptide (CLIP) region-mediated binding of invariant chain (Ii) to DP, allowing endoplasmic reticulum (ER)-resident endogenous antigens to constitutively associate with DP84Gly such as DP4...
March 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29546878/inflammation-induces-two-types-of-inflammatory-dendritic-cells-in-inflamed-lymph-nodes
#14
Jiyoun Min, Dongchan Yang Sung, Mirang Kim, Keeok Haam, Anji Yoo, Jae-Hoon Choi, Barbara U Schraml, Yong Sung Kim, Dongsup Kim, Suk-Jo Kang
The spatiotemporal regulation of immune cells in lymph nodes (LNs) is crucial for mounting protective T-cell responses, which are orchestrated by dendritic cells (DCs). However, it is unclear how the DC subsets are altered by the inflammatory milieu of LNs. Here, we show that the inflamed LNs of Listeria-infected mice are characterized by the clustering of neutrophils and monocytes and IFN-γ production. Significantly, the early inflammatory responses are coupled with the differentiation of not one, but two types of CD64+ CD11c+ MHCII+ inflammatory DCs...
March 16, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29507342/cancer-associated-fibroblasts-induce-antigen-specific-deletion-of-cd8-t-cells-to-protect-tumour-cells
#15
Matthew A Lakins, Ehsan Ghorani, Hafsa Munir, Carla P Martins, Jacqueline D Shields
Tumours have developed strategies to interfere with most steps required for anti-tumour immune responses. Although many populations contribute to anti-tumour responses, tumour-infiltrating cytotoxic T cells dominate, hence, many suppressive strategies act to inhibit these. Tumour-associated T cells are frequently restricted to stromal zones rather than tumour islands, raising the possibility that the tumour microenvironment, where crosstalk between malignant and "normal" stromal cells exists, may be critical for T cell suppression...
March 5, 2018: Nature Communications
https://www.readbyqxmd.com/read/29507107/clec9a-dendritic-cells-are-not-essential-for-antitumor-cd8-t-cell-responses-induced-by-poly-i-c-immunotherapy
#16
Connie B Gilfillan, Sabine Kuhn, Camille Baey, Evelyn J Hyde, Jianping Yang, Christiane Ruedl, Franca Ronchese
In the steady state, tumors harbor several populations of dendritic cells (DCs) and myeloid cells that are key regulators of the intratumoral immune environment. Among these cells, migratory CD103+ cross-presenting DCs are thought to be critical for tumor-specific CTL responses and tumor resistance. However, it is unclear whether this prominent role also extends to immunotherapy. We used a murine orthotopic mammary tumor model, as well as Clec9A-diphtheria toxin receptor mice that can be depleted of the specialized cross-presenting CD8α+ and CD103+ DC1 subsets, to investigate the role of these DCs in immunotherapy...
March 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29493121/endolysosomal-escape-nanovaccines-through-adjuvant-induced-tumor-antigen-assembly-for-enhanced-effector-cd8-t-cell-activation
#17
Liping Qiu, Michael Valente, Yusuf Dolen, Eliezer Jäger, Martin Ter Beest, Liyan Zheng, Carl G Figdor, Martijn Verdoes
The activation of tumor-specific effector immune cells is key for successful immunotherapy and vaccination is a powerful strategy to induce such adaptive immune responses. However, the generation of effective anticancer vaccines is challenging. To overcome these challenges, a novel straight-forward strategy of adjuvant-induced tumor antigen assembly to generate nanovaccines with superior antigen/adjuvant loading efficiency is developed. To protect nanovaccines in circulation and to introduce additional functionalities, a biocompatible polyphenol coating is installed...
March 1, 2018: Small
https://www.readbyqxmd.com/read/29490164/regulation-of-the-cell-biology-of-antigen-cross-presentation
#18
J Magarian Blander
Antigen cross-presentation is an adaptation of the cellular process of loading MHC-I molecules with endogenous peptides during their biosynthesis within the endoplasmic reticulum. Cross-presented peptides derive from internalized proteins, microbial pathogens, and transformed or dying cells. The physical separation of internalized cargo from the endoplasmic reticulum, where the machinery for assembling peptide-MHC-I complexes resides, poses a challenge. To solve this problem, deliberate rewiring of organelle communication within cells is necessary to prepare for cross-presentation, and different endocytic receptors and vesicular traffic patterns customize the emergent cross-presentation compartment to the nature of the peptide source...
February 28, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29485973/self-adjuvanting-nanoemulsion-targeting-dendritic-cell-receptor-clec9a-enables-antigen-specific-immunotherapy
#19
Bijun Zeng, Anton Pj Middelberg, Adrian Gemiarto, Kelli MacDonald, Alan G Baxter, Meghna Talekar, Davide Moi, Kirsteen M Tullett, Irina Caminschi, Mireille H Lahoud, Roberta Mazzieri, Riccardo Dolcetti, Ranjeny Thomas
Non-antigen-specific stimulatory cancer immunotherapies are commonly complicated by off-target effects. Antigen-specific immunotherapy, combining viral tumor antigen or personalised neo-epitopes with immune targeting, offers a solution. However, the lack of flexible systems targeting tumor antigens to cross-presenting dendritic cells (DCs) limits clinical development. Although antigen-anti-CLEC-9A mAb conjugates target cross-presenting DCs, adjuvant must be co-delivered for cytotoxic T-cell (CTL) induction...
February 27, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29477971/in-vitro-uptake-of-oligomannose-coated-liposomes-leads-to-differentiation-of-inflammatory-monocytes-into-mature-antigen-presenting-cells-that-can-activate-t-cells
#20
Yuko Matsuoka, Yoko Kawauchi, Yasuhiro Kuroda, Kiyotaka Kawauchi, Naoya Kojima
Oligomannose-coated liposomes (OMLs), containing entrapped antigens, serve as effective antigen delivery vehicles and as a novel adjuvant to induce antigen-specific cellular immune responses. However, in vitro activation of antigen-presenting cells (APCs) by OMLs has not yet been demonstrated. In this paper, we found that OMLs can deliver the antigens and the stimulatory signals into inflammatory monocytes in vitro, leading to differentiation of the cells to mature APCs. When OMLs were co-cultured with peripheral blood mononuclear cells from C57BL/6 mice in the presence of mouse serum, OMLs were preferentially incorporated into both Ly6Chigh monocytes and Ly6Clow monocytes, which are referred to as murine inflammatory and resident monocytes, respectively...
February 22, 2018: International Immunopharmacology
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