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Immunological synapse

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https://www.readbyqxmd.com/read/29789661/a-correlative-and-quantitative-imaging-approach-enabling-characterization-of-primary-cell-cell-communication-case-of-human-cd4-t-cell-macrophage-immunological-synapses
#1
Richard Kasprowicz, Emma Rand, Peter J O'Toole, Nathalie Signoret
Cell-to-cell communication engages signaling and spatiotemporal reorganization events driven by highly context-dependent and dynamic intercellular interactions, which are difficult to capture within heterogeneous primary cell cultures. Here, we present a straightforward correlative imaging approach utilizing commonly available instrumentation to sample large numbers of cell-cell interaction events, allowing qualitative and quantitative characterization of rare functioning cell-conjugates based on calcium signals...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29757266/spatial-and-temporal-control-of-t-cell-activation-using-a-photoactivatable-agonist
#2
Elisa Sanchez, Morgan Huse
T lymphocytes engage in rapid, polarized signaling, occurring within minutes following TCR activation. This induces formation of the immunological synapse, a stereotyped cell-cell junction that regulates T cell activation and directionally targets effector responses. To study these processes effectively, an imaging approach that is tailored to capturing fast, polarized responses is necessary. This protocol describes such a system, which is based on a photoactivatable peptide-major histocompatibility complex (pMHC) that is non-stimulatory until it is exposed to ultraviolet light...
April 25, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29751004/mutations-affecting-the-actin-regulator-wdr1-lead-to-aberrant-lymphoid-immunity
#3
Laurène Pfajfer, Nina K Mair, Raúl Jiménez-Heredia, Ferah Genel, Nesrin Gulez, Ömür Ardeniz, Birgit Hoeger, Sevgi Köstel Bal, Christoph Madritsch, Artem Kalinichenko, Rico Chandra Ardy, Bengü Gerçeker, Javier Rey-Barroso, Hanna Ijspeert, Stuart G Tangye, Ingrid Simonitsch-Klupp, Johannes B Huppa, Mirjam van der Burg, Loïc Dupré, Kaan Boztug
BACKGROUND: The actin-interacting protein WDR1 promotes cofilin-dependent actin filament turnover. Biallelic WDR1 mutations have recently been identified in an immunodeficiency/autoinflammatory syndrome with aberrant morphology and function of myeloid cells. OBJECTIVE: Given the pleiotropic expression of WDR1, we here investigated to what extent it might control the lymphoid arm of the immune system in humans. METHODS: Histological and detailed immunological analyses were performed to elucidate the role of WDR1 in development and function of B and T lymphocytes...
May 8, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29749649/transgelin-2-in-immunity-its-implication-in-cell-therapy
#4
REVIEW
Suin Jo, Hye-Ran Kim, YeVin Mun, Chang-Duk Jun
Transgelin-2 is a small 22-kDa actin-binding protein implicated in actin dynamics, which stabilizes actin structures and participates in actin-associated signaling pathways. Much curiosity regarding transgelin-2 has centered around its dysregulation in tumor development and associated diseases. However, recent studies have shed new light on the functions of transgelin-2, the only transgelin family member present in leukocytes, in the context of various immune responses. In this review, we outlined the biochemical properties of transgelin-2 and its physiological functions in T cells, B cells, and macrophages...
May 11, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29749611/proteomic-definition-of-human-mucosal-associated-invariant-t-cells-determines-their-unique-molecular-effector-phenotype
#5
Björn Bulitta, Werner Zuschratter, Isabel Bernal, Dunja Bruder, Frank Klawonn, Martin von Bergen, Henrikus Stephanus Paulus Garritsen, Lothar Jänsch
Mucosal-associated invariant T cells (MAIT) constitute the most abundant anti-bacterial CD8+ T cell population in humans. MR1/TCR-activated MAIT cells were reported to organize cytotoxic and innate-like responses but knowledge about their molecular effector phenotype is still fragmentary. Here, we have examined the functional inventory of human MAIT cells (CD3+Vα7.2+CD161+) in comparison with those from conventional non-MAIT CD8+ T cells (cCD8+ ) and NK cells. Quantitative mass spectrometry characterized 5500 proteins of primary MAIT cells and identified 160 and 135 proteins that discriminate them from cCD8+ T cells and NK cells donor-independently...
May 11, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29741477/empty-conformers-of-hla-b-preferentially-bind-cd8-and-regulate-cd8-t-cell-function
#6
Jie Geng, John D Altman, Sujatha Krishnakumar, Malini Raghavan
When complexed with antigenic peptides, human leukocyte antigen (HLA) class I (HLA-I) molecules initiate CD8+ T cell responses via interaction with the T cell receptor (TCR) and co-receptor CD8. Peptides are generally critical for the stable cell surface expression of HLA-I molecules. However, for HLA-I alleles such as HLA-B*35:01, peptide-deficient (empty) heterodimers are thermostable and detectable on the cell surface. Additionally, peptide-deficient HLA-B*35:01 tetramers preferentially bind CD8 and to a majority of blood-derived CD8+ T cells via a CD8-dependent binding mode...
May 9, 2018: ELife
https://www.readbyqxmd.com/read/29725325/mitochondria-an-organelle-of-bacterial-origin-controlling-inflammation
#7
REVIEW
Alain Meyer, Gilles Laverny, Livio Bernardi, Anne Laure Charles, Ghada Alsaleh, Julien Pottecher, Jean Sibilia, Bernard Geny
Inflammation is a cellular and molecular response to infection and/or tissues injury. While a suited inflammatory response in intensity and time allows for killing pathogens, clearing necrotic tissue, and healing injury; an excessive inflammatory response drives various diseases in which inflammation and tissues damages/stress self-sustain each other. Microbes have been poorly implied in non-resolving inflammation, emphasizing the importance of endogenous regulation of inflammation. Mitochondria have been historically identified as the main source of cellular energy, by coupling the oxidation of fatty acids and pyruvate with the production of high amount of adenosine triphosphate by the electron transport chain...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29686427/a-mobile-endocytic-network-connects-clathrin-independent-receptor-endocytosis-to-recycling-and-promotes-t-cell-activation
#8
Ewoud B Compeer, Felix Kraus, Manuela Ecker, Gregory Redpath, Mayan Amiezer, Nils Rother, Philip R Nicovich, Natasha Kapoor-Kaushik, Qiji Deng, Guerric P B Samson, Zhengmin Yang, Jieqiong Lou, Michael Carnell, Haig Vartoukian, Katharina Gaus, Jérémie Rossy
Endocytosis of surface receptors and their polarized recycling back to the plasma membrane are central to many cellular processes, such as cell migration, cytokinesis, basolateral polarity of epithelial cells and T cell activation. Little is known about the mechanisms that control the organization of recycling endosomes and how they connect to receptor endocytosis. Here, we follow the endocytic journey of the T cell receptor (TCR), from internalization at the plasma membrane to recycling back to the immunological synapse...
April 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29679656/pd-1-blocks-lytic-granule-polarization-with-concomitant-impairment-of-integrin-outside-in-signaling-in-natural-killer-cell-immunological-synapse
#9
Yu Huang, Zhiying Chen, Joon Hee Jang, Mirza S Baig, Grant Bertolet, Casey Schroeder, Shengjian Huang, Qian Hu, Yong Zhao, Dorothy E Lewis, Lidong Qin, Michael Xi Zhu, Dongfang Liu
BACKGROUND: Inhibitory receptor programmed cell death protein-1 (PD-1) is upregulated on a variety of immune cells, including natural killer (NK) cells, during chronic virus infection and tumorigenesis. Blockade of PD-1 or its ligands produces durable clinical responses with tolerable side effects in patients with a broad spectrum of cancers. However, the underlying molecular mechanisms of how PD-1 regulates NK cell function remain poorly characterized. OBJECTIVE: We sought to determine what effect PD-1 signaling has on NK cells...
April 18, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29668063/beyond-migration-chemokines-in-lymphocyte-priming-differentiation-and-modulating-effector-functions
#10
REVIEW
Julia M Laufer, Daniel F Legler
Chemokines and their receptors coordinate the positioning of leukocytes, and lymphocytes in particular, in space and time. Discrete lymphocyte subsets, depending on their activation and differentiation status, express various sets of chemokine receptors to be recruited to distinct tissues. Thus, the network of chemokines and their receptors ensures the correct localization of specialized lymphocyte subsets within the appropriate microenvironment enabling them to search for cognate antigens, to become activated, and to fulfill their effector functions...
April 18, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29656550/mir-181c-brk1-axis-plays-a-key-role-in-actin-cytoskeleton-dependent-t-cell-function
#11
Shok Ping Lim, Nikolaos Ioannou, Alan G Ramsay, David Darling, Joop Gäken, Ghulam J Mufti
MicroRNAs are short endogenous noncoding RNAs that play pivotal roles in a diverse range of cellular processes. The miR-181 family is important in T cell development, proliferation, and activation. In this study, we have identified BRK1 as a potential target of miR-181c using a dual selection functional assay and have showed that miR-181c regulates BRK1 by translational inhibition. Given the importance of miR-181 in T cell function and the potential role of BRK1 in the involvement of WAVE2 complex and actin polymerization in T cells, we therefore investigated the influence of miR-181c-BRK1 axis in T cell function...
April 14, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29652923/limited-immune-surveillance-in-lymphoid-tissue-by-cytolytic-cd4-t-cells-during-health-and-hiv-disease
#12
Marcus Buggert, Son Nguyen, Laura M McLane, Maria Steblyanko, Nadia Anikeeva, Dominic Paquin-Proulx, Perla M Del Rio Estrada, Yuria Ablanedo-Terrazas, Kajsa Noyan, Morgan A Reuter, Korey Demers, Johan Sandberg, Michael A Eller, Hendrik Streeck, Marianne Jansson, Piotr Nowak, Anders Sönnerborg, David H Canaday, Ali Naji, E John Wherry, Merlin Robb, Steven G Deeks, Gustavo Reyes-Teran, Yuri Sykulev, Annika C Karlsson, Michael R Betts
CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cell populations expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes)...
April 13, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29557634/spatial-and-chemical-surface-guidance-of-nk-cell-cytotoxic-activity
#13
Guillaume Le Saux, Avishay Edri, Yossi Keydar, Uzi Hadad, Angel Porgador, Mark Schvartzman
Studying how different signaling pathways spatially integrate in cells requires selective manipulation and control of different transmembrane ligand-receptor pairs at the same time. This work explores a novel method for precisely arranging two arbitrarily chosen ligands on a micron-scale two-dimensional pattern. The approach is based on lithographic patterning of Au and TiO2 films, followed by their selective functionalization with Ni-nitrilotriacetic acid-histidine and biotin-avidin chemistries, respectively...
April 11, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29515578/mechanisms-for-cell-to-cell-transmission-of-hiv-1
#14
REVIEW
Lucie Bracq, Maorong Xie, Serge Benichou, Jérôme Bouchet
While HIV-1 infection of target cells with cell-free viral particles has been largely documented, intercellular transmission through direct cell-to-cell contact may be a predominant mode of propagation in host. To spread, HIV-1 infects cells of the immune system and takes advantage of their specific particularities and functions. Subversion of intercellular communication allows to improve HIV-1 replication through a multiplicity of intercellular structures and membrane protrusions, like tunneling nanotubes, filopodia, or lamellipodia-like structures involved in the formation of the virological synapse...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29508283/ad-related-n-terminal-truncated-tau-is-sufficient-to-recapitulate-in-vivo-the-early-perturbations-of-human-neuropathology-implications-for-immunotherapy
#15
A Borreca, V Latina, V Corsetti, S Middei, S Piccinin, F Della Valle, R Bussani, M Ammassari-Teule, R Nisticò, P Calissano, G Amadoro
The NH2 tau 26-44 aa (i.e., NH2 htau) is the minimal biologically active moiety of longer 20-22-kDa NH2 -truncated form of human tau-a neurotoxic fragment mapping between 26 and 230 amino acids of full-length protein (htau40)-which is detectable in presynaptic terminals and peripheral CSF from patients suffering from AD and other non-AD neurodegenerative diseases. Nevertheless, whether its exogenous administration in healthy nontransgenic mice is able to elicit a neuropathological phenotype resembling human tauopathies has not been yet investigated...
March 5, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29503199/immunological-synapse-predicts-effectiveness-of-chimeric-antigen-receptor-cells
#16
Wei Xiong, Yuhui Chen, Xi Kang, Zhiying Chen, Peilin Zheng, Yi-Hsin Hsu, Joon Hee Jang, Lidong Qin, Hao Liu, Gianpietro Dotti, Dongfang Liu
Chimeric antigen receptor (CAR)-modified T cell therapy has the potential to improve the overall survival of patients with malignancies by enhancing the effectiveness of CAR T cells. Precisely predicting the effectiveness of various CAR T cells represents one of today's key unsolved problems in immunotherapy. Here, we predict the effectiveness of CAR-modified cells by evaluating the quality of the CAR-mediated immunological synapse (IS) by quantitation of F-actin, clustering of tumor antigen, polarization of lytic granules (LGs), and distribution of key signaling molecules within the IS...
April 4, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29462581/immunology-is-actin-at-the-lytic-synapse-a-friend-or-a-foe
#17
John A Hammer
Cytotoxic T cells and natural killer cells defend us against disease by secreting lytic granules. Whether actin facilitates or thwarts lytic granule secretion has been an open question. Recent results now indicate that the answer depends on the maturation stage of the immune cell-target cell contact.
February 19, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29410223/spatio-temporal-image-correlation-spectroscopy-and-super-resolution-microscopy-to-quantify-molecular-dynamics-in-t-cells
#18
REVIEW
George W Ashdown, Dylan M Owen
Many cellular processes are regulated by the spatio-temporal organisation of signalling complexes, cytoskeletal components and membranes. One such example is at the T cell immunological synapse where the retrograde flow of cortical filamentous (F)-actin from the synapse periphery drives signalling protein microclusters towards the synapse centre. The density of this mesh however, makes visualisation and analysis of individual actin fibres difficult due to the resolution limit of conventional microscopy. Recently, super-resolution methods such as structured illumination microscopy (SIM) have surpassed this resolution limit...
February 2, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29403502/integrins-modulate-t-cell-receptor-signaling-by-constraining-actin-flow-at-the-immunological-synapse
#19
Katarzyna I Jankowska, Edward K Williamson, Nathan H Roy, Daniel Blumenthal, Vidhi Chandra, Tobias Baumgart, Janis K Burkhardt
Full T cell activation requires coordination of signals from multiple receptor-ligand pairs that interact in parallel at a specialized cell-cell contact site termed the immunological synapse (IS). Signaling at the IS is intimately associated with actin dynamics; T cell receptor (TCR) engagement induces centripetal flow of the T cell actin network, which in turn enhances the function of ligand-bound integrins by promoting conformational change. Here, we have investigated the effects of integrin engagement on actin flow, and on associated signaling events downstream of the TCR...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29398219/nanoscale-dynamism-of-actin-enables-secretory-function-in-cytolytic-cells
#20
Alexandre F Carisey, Emily M Mace, Mezida B Saeed, Daniel M Davis, Jordan S Orange
Natural killer (NK) cells are innate immune effectors that lyse virally infected and tumorigenic cells through the formation of an immunological synapse. Actin remodeling at the lytic immunological synapse is a critical requirement for multiple facets of cytotoxic function. Activating receptor and integrin signaling leads to the regulated turnover and remodeling of actin, which is required for adhesion, sustained receptor signaling, and ultimately exocytosis. NK cells undergo lytic granule exocytosis in hypodense regions of a pervasive actin network...
February 19, 2018: Current Biology: CB
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