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Cross-presentation

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https://www.readbyqxmd.com/read/29158474/unc93b1-interacts-with-the-calcium-sensor-stim1-for-efficient-antigen-cross-presentation-in-dendritic-cells
#1
Sophia Maschalidi, Paula Nunes-Hasler, Clarissa R Nascimento, Ignacio Sallent, Valérie Lannoy, Meriem Garfa-Traore, Nicolas Cagnard, Fernando E Sepulveda, Pablo Vargas, Ana-Maria Lennon-Duménil, Peter van Endert, Thierry Capiod, Nicolas Demaurex, Guillaume Darrasse-Jèze, Bénédicte Manoury
Dendritic cells (DC) have the unique ability to present exogenous antigens via the major histocompatibility complex class I pathway to stimulate naive CD8(+) T cells. In DCs with a non-functional mutation in Unc93b1 (3d mutation), endosomal acidification, phagosomal maturation, antigen degradation, antigen export to the cytosol and the function of the store-operated-Ca(2+)-entry regulator STIM1 are impaired. These defects result in compromised antigen cross-presentation and anti-tumor responses in 3d-mutated mice...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29147022/conventional-cd4-t-cells-present-bacterial-antigens-to-induce-cytotoxic-and-memory-cd8-t-cell-responses
#2
Aránzazu Cruz-Adalia, Guillermo Ramirez-Santiago, Jesús Osuna-Pérez, Mónica Torres-Torresano, Virgina Zorita, Ana Martínez-Riaño, Viola Boccasavia, Aldo Borroto, Gloria Martínez Del Hoyo, José María Gozález-Granado, Balbino Alarcón, Francisco Sánchez-Madrid, Esteban Veiga
Bacterial phagocytosis and antigen cross-presentation to activate CD8(+) T cells are principal functions of professional antigen presenting cells. However, conventional CD4(+) T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8(+) T cells, which proliferate and become cytotoxic in response. CD4(+) T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8(+) T cells with low PD-1 expression...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29144754/immunogenic-cell-death-amplified-by-co-localized-adjuvant-delivery-for-cancer-immunotherapy
#3
Yuchen Fan, Rui Kuai, Yao Xu, Lukasz J Ochyl, Darrell J Irvine, James J Moon
Despite their potential, conventional whole-cell cancer vaccines prepared by freeze-thawing or irradiation have shown limited therapeutic efficacy in clinical trials. Recent studies have indicated that cancer cells treated with certain chemotherapeutics, such as mitoxantrone, can undergo immunogenic cell death (ICD) and initiate antitumor immune responses. However, it remains unclear how to exploit ICD for cancer immunotherapy. Here, we present a new material-based strategy for converting immunogenically dying tumor cells into a powerful platform for cancer vaccination and demonstrate their therapeutic potential in murine models of melanoma and colon carcinoma...
November 22, 2017: Nano Letters
https://www.readbyqxmd.com/read/29142130/effective-priming-of-hsv-specific-cd8-t-cells-in-vivo-does-not-require-infected-dendritic-cells
#4
Paul G Whitney, Christina Makhlouf, Beth MacLeod, Joel Z Ma, Elise Gressier, Marie Greyer, Katharina Hochheiser, Annabell Bachem, Ali Zaid, David Voehringer, William R Heath, Mayura V Wagle, Ian Parish, Tiffany A Russell, Stewart A Smith, David C Tscharke, Thomas Gebhardt, Sammy Bedoui
Resolution of virus infections depends on the priming of virus-specific CD8(+) T cells by dendritic cells (DC). While this process requires MHC class I-restricted antigen presentation by DC, the relative contribution to CD8(+) T cell priming by infected DC is less clear. We have addressed this question in the context of a peripheral infection with herpes simplex virus type 1 (HSV). Assessing the endogenous, polyclonal HSV-specific CD8(+) T cell response, we found that effective in vivo T cell priming depended on the presence of DC subsets specialized in cross-presentation while Langerhans cells and plasmacytoid DC were dispensable...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29128232/liposome-based-immunity-inducing-systems-for-cancer-immunotherapy
#5
REVIEW
Eiji Yuba
Cancer immunotherapy has gained much attention for next-generation cancer treatment. To conduct cancer immunotherapy, efficient antigen delivery systems must be able to deliver an antigen selectively to antigen-presenting cells, release it at suitable sites for induction of cross-presentation, and simultaneously induce activation of immunocompetent cells. Liposomes are a candidate for use as such multifunctional antigen delivery carriers because of their capability for easy functionalization. This review describes the rational design of liposome-based antigen delivery systems...
November 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29126597/role-of-autophagy-in-mhc-class-i-restricted-antigen-presentation
#6
Luc Van Kaer, Vrajesh V Parekh, J Luke Postoak, Lan Wu
Major histocompatibility complex (MHC) class I molecules present peptide antigens to MHC class I-restricted CD8(+) T lymphocytes. The peptides loaded onto MHC class I molecules are typically derived from cytosolic antigens, which includes both self and foreign proteins. In addition to this classical MHC class I antigen presentation pathway, some cell types, especially dendritic cells can present antigens from exogenous sources to MHC class I-restricted CD8(+) T cells, in a process called cross-presentation...
November 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29100330/protective-cellular-immunity-generated-by-cross-presenting-recombinant-overlapping-peptide-proteins
#7
Lili Cai, Jianbo Zhang, Renying Zhu, Weixing Shi, Xiaobing Xia, Mark Edwards, William Finch, Anthony Coombs, Ju Gao, Kangwen Chen, Sophie Owen, Shisong Jiang, Wenshu Lu
Priming of naive CD8(+) and CD4(+) T cells by dendritic cells (DCs) requires effective antigen presentation on both MHC class I and II molecules. We have developed a novel technology to use recombinant overlapping peptides (ROP) that stimulate both CD8(+) and CD4(+) T cell immune responses. The single chain protein of a ROP is made up of overlapping peptides linked by the target sequence (LRMK) for cathepsin S, a protease found in the endosomes of DCs. We designed synthetic genes encoding ROPs derived from ovalbumin (OVA), tuberculosis protein (CFP10-ESAT6), human papilloma virus (HPV) protein (E7) and survivin, a protein commonly over-expressed in tumour cells...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29091760/a-discrete-subset-of-monocyte-derived-cells-among-typical-conventional-type-2-dendritic-cells-can-efficiently-cross-present
#8
Jianpeng Sheng, Qi Chen, Irene Soncin, See Liang Ng, Klaus Karjalainen, Christiane Ruedl
Dendritic cells (DCs) and macrophages (Mϕs) share close developmental pathways and functional features, leading to blurring of the boundaries between these two cell lineages. However, a deeper understanding of DC and Mϕ ontogeny and more refined phenotypic and functional characterizations have helped to delineate pre-DC-derived conventional DCs (cDCs), including cDC1s and cDC2s, from monocyte-derived Mϕs. Here, we further refine DC/Mϕ cell classification and report that classically defined cDC2s contain a discrete population of monocyte-derived migratory antigen-presenting cells with Mϕ phenotype but functional DC features, including cross-presentation...
October 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/29079107/dissecting-antigen-processing-and-presentation-routes-in-dermal-vaccination-strategies
#9
Anouk C M Platteel, Sandrine Henri, Dietmar M Zaiss, Alice J A M Sijts
The skin is an attractive site for vaccination due to its accessibility and presence of immune cells surveilling this barrier. However, knowledge of antigen processing and presentation upon dermal vaccination is sparse. In this study we determined antigen processing routes that lead to CD8(+) T cell activation following dermal DNA tattoo immunization, exploiting a model antigen that contains an immunoproteasome-dependent epitope. In agreement with earlier reports, we found that DNA tattoo immunization of wild type (WT) mice triggered vigorous responses to the immunoproteasome-dependent model epitope, whereas gene-deficient mice lacking the immunoproteasome subunits β5i/LMP7 and β2i/MECL1 failed to respond...
October 24, 2017: Vaccine
https://www.readbyqxmd.com/read/29070650/interleukin-12-from-cd103-batf3-dependent-dendritic-cells-required-for-nk-cell-suppression-of-metastasis
#10
Deepak Mittal, Dipti Vijayan, Eva M Putz, Amelia R Aguilera, Kate A Markey, Jasmin Straube, Stephen Kazakoff, Stephen L Nutt, Kazuyoshi Takeda, Geoffrey R Hill, Nicola Waddell, Mark J Smyth
Several host factors may affect the spread of cancer to distant organs, however the intrinsic role of dendritic cells (DCs) in controlling metastasis is poorly described. Here we show in several tumor models that although the growth of primary tumors in Batf3-deficient mice, which lack cross-presenting DCs, was not different from primary tumors in wild-type (WT) control mice, Batf-deficient mice had increased experimental and spontaneous metastasis and poorer survival. The increased metastasis was independent of CD4+ and CD8+ T lymphocytes, but required NK cells and IFNγ...
October 25, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29062313/dead-tumor-cells-expressing-infectious-salmon-anemia-virus-fusogenic-protein-favor-antigen-cross-priming-in-vitro
#11
Jonathan Morales, Carlos Barrera-Avalos, Carlos Castro, Stephanie Castillo, Claudio Barrientos, Claudia Robles-Planells, Ximena López, Ernesto Torres, Margarita Montoya, Marcelo Cortez-San Martín, Denise Riquelme, Alejandro Escobar, Ricardo Fernández, Mónica Imarai, Daniela Sauma, Leonel E Rojo, Elias Leiva-Salcedo, Claudio Acuña-Castillo
Antigen cross-presentation is a crucial step in the assembly of an antitumor immune response leading to activation of naïve CD8 T cells. This process has been extensively used in clinical trials, in which dendritic cells generated in vitro are loaded with tumor antigens and then autotransplanted to the patients. Recently, the use of autologous transplant of dendritic cells fused with dying tumor cells has demonstrated good results in clinical studies. In this work, we generated a similar process in vivo by treating mice with dead tumor cells [cell bodies (CBs)] expressing the fusogenic protein of the infectious salmon anemia virus (ISAV)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29051851/biomimetically-engineered-demi-bacteria-potentiate-vaccination-against-cancer
#12
Dezhi Ni, Shuang Qing, Hui Ding, Hua Yue, Di Yu, Shuang Wang, Nana Luo, Zhiguo Su, Wei Wei, Guanghui Ma
Failure in enhancing antigen immunogenicity has limited the development of cancer vaccine. Inspired by effective immune responses toward microorganisms, demi-bacteria (DB) from Bacillus are engineered as carriers for cancer vaccines. The explored hydrothermal treatment enables the Bacillus to preserve optimal pathogen morphology with intrinsic mannose receptor agonist. Meanwhile, the treated Bacillus can be further endowed with ideal hollow/porous structure for efficient accommodation of antigen and adjuvant, such as CpG...
October 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/29046894/fatty-acid-mimetic-micelles-for-dual-delivery-of-antigens-and-imidazoquinoline-adjuvants
#13
Sema Sevimli, Frances C Knight, Pavlo Gilchuk, Sebastian Joyce, John T Wilson
Vaccine design has undergone a shift towards the use of purified protein subunit vaccines, which offer increased safety and greater control over antigen specificity, but at the expense of immunogenicity. Here we report the development of a new polymer-based vaccine delivery platform engineered to enhance immunity through the co-delivery of protein antigens and the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ). Owing to the preferential solubility of IMQ in fatty acids, a series of block copolymer micelles with a fatty acid-mimetic core comprising lauryl methacrylate (LMA) and methacrylic acid (MAA), and a poly(ethylene glycol) methyl ether methacrylate (PEGMA) corona decorated with pyridyl disulfide ethyl methacrylate (PDSM) moieties for antigen conjugation were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization...
February 13, 2017: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/28993771/tumor-derived-microvesicles-modulate-antigen-cross-processing-via-reactive-oxygen-species-mediated-alkalinization-of-phagosomal-compartment-in-dendritic-cells
#14
Federico Battisti, Chiara Napoletano, Hassan Rahimi Koshkaki, Francesca Belleudi, Ilaria Grazia Zizzari, Ilary Ruscito, Sara Palchetti, Filippo Bellati, Pierluigi Benedetti Panici, Maria Rosaria Torrisi, Giulio Caracciolo, Fabio Altieri, Marianna Nuti, Aurelia Rughetti
Dendritic cells (DCs) are the only antigen-presenting cells able to prime naïve T cells and cross-prime antigen-specific CD8(+) T cells. Their functionality is a requirement for the induction and maintenance of long-lasting cancer immunity. Albeit intensively investigated, the in vivo mechanisms underlying efficient antigen cross-processing and presentation are not fully understood. Several pieces of evidence indicate that antigen transfer to DCs mediated by microvesicles (MVs) enhances antigen immunogenicity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28963110/development-diversity-and-function-of-dendritic-cells-in-mouse-and-human
#15
David A Anderson, Kenneth M Murphy, Carlos G Briseño
The study of murine dendritic cell (DC) development has been integral to the identification of specialized DC subsets that have unique requirements for their form and function. Advances in the field have also provided a framework for the identification of human DC counterparts, which appear to have conserved mechanisms of development and function. Multiple transcription factors are expressed in unique combinations that direct the development of classical DCs (cDCs), which include two major subsets known as cDC1s and cDC2s, and plasmacytoid DCs (pDCs)...
September 29, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28961609/dcone-as-an-allogeneic-cell-based-vaccine-for-multiple-myeloma
#16
Rebecca Karp Leaf, Dina Stroopinsky, Athalia R Pyzer, Ada M Kruisbeek, Sandra van Wetering, Abigail Washington, Adam Ephraim, Leandra Cole, Adam Morin, Salvia Jain, Myrna R Nahas, Arik Apel, Jon Arnason, Ayad Hamdan, Jacalyn Rosenblatt, David Avigan
Multiple myeloma (MM) is characterized by progressive immune dysregulation, loss of myeloma-specific immunity, and an immunosuppressive milieu that fosters disease growth and immune escape. Accordingly, cancer vaccines that reverse tumor-associated immune suppression represent a promising therapeutic avenue of investigation. We examined the potential of an allogeneic cellular vaccine to generate immune responses against MM tumor cells. The DCOne vaccine is comprised of a human myeloid leukemia cell line differentiated into a fully functional dendritic cell, expressing a range of tumor-associated antigens that are also known targets in MM...
November 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28960134/differential-requirement-of-rab22a-for-the-recruitment-of-er-derived-proteins-to-phagosomes-and-endosomes-in-dendritic-cells
#17
Cristina Croce, Luis S Mayorga, Ignacio Cebrian
The recruitment of endoplasmic reticulum (ER) components to dendritic cell (DC) phagosomes and endosomes is a crucial event to achieve efficient cross-presentation of exogenous antigens. We have previously identified the small GTPase Rab22a as a key regulator of MHC-I trafficking and antigen cross-presentation by DCs. In this study we show that low expression of Rab22a does not prevent the normal delivery of ER-derived proteins to DC phagosomes. In contrast, the presence of these proteins was diminished in endosomes labelled with a fluid phase marker...
September 29, 2017: Small GTPases
https://www.readbyqxmd.com/read/28959385/dominant-immunosuppression-of-dendritic-cell-function-by-prostate-cancer-derived-exosomes
#18
Josephine Salimu, Jason Webber, Mark Gurney, Saly Al-Taei, Aled Clayton, Zsuzsanna Tabi
Exosomes are a distinct population of extracellular vesicles of endocytic origin with a protein repertoire similar to the parent cell. Although tumour-derived exosomes harbour immunosuppressive characteristics, they also carry tumour antigens and thus potentially contribute to immune activation. The aim of this study was to examine the impact of prostate cancer exosomes on tumour antigen cross-presentation. DU145 cells, transduced with shRNA to knockdown Rab27a (DU145(KD)) that inhibits exosome secretion, triggered significantly stronger tumour-antigen-specific T cell responses when loaded onto dendritic cells (DC) than control DU145 cells...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28959259/transmembrane-helices-are-an-overlooked-source-of-major-histocompatibility-complex-class-i-epitopes
#19
Frans Bianchi, Johannes Textor, Geert van den Bogaart
About a fourth of the human proteome is anchored by transmembrane helices (TMHs) to lipid membranes. TMHs require multiple hydrophobic residues for spanning membranes, and this shows a striking resemblance with the requirements for peptide binding to major histocompatibility complex (MHC) class I. It, therefore, comes as no surprise that bioinformatics analysis predicts an over-representation of TMHs among strong MHC class I (MHC-I) binders. Published peptide elution studies confirm that TMHs are indeed presented by MHC-I...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28947859/modulation-of-dendritic-cell-apoptosis-and-cd8-cytotoxicity-by-histamine-role-of-protein-kinase-c
#20
Julieta Alcain, Enrique Podaza, María Soledad Gori, Gabriela Salamone, Mónica Vermeulen
Dendritic cells (DC) are able to present extracellular antigens associated with the molecules of the major histocompatibility complex class I. In a previous work, we demonstrated that the histamine (HIS), acting through H1/H4 receptors, increases the cross-presentation of soluble ovalbumin by murine DC and can enhance the recruitment of specific CD8(+) T lymphocytes during the development of chronic inflammatory responses. Here, we studied in more depth the mechanisms underlying this enhancement. We showed that the cytotoxicity of specific CD8(+) lymphocytes is increased in HIS-treated DC and it is lost by inhibition of vacuolar-ATPase that prevents endosome acidification...
2017: Mediators of Inflammation
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