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Immunological synapse

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https://www.readbyqxmd.com/read/28205652/bridging-the-gap-microfluidic-devices-for-short-and-long-distance-cell-cell-communication
#1
REVIEW
Timothy Quang Vu, Ricardo Miguel Bessa de Castro, Lidong Qin
Cell-cell communication is a crucial component of many biological functions. For example, understanding how immune cells and cancer cells interact, both at the immunological synapse and through cytokine secretion, can help us understand and improve cancer immunotherapy. The study of how cells communicate and form synaptic connections is important in neuroscience, ophthalmology, and cancer research. But in order to increase our understanding of these cellular phenomena, better tools need to be developed that allow us to study cell-cell communication in a highly controlled manner...
February 16, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28202613/the-activating-human-nk-cell-receptor-kir2ds2-recognizes-a-%C3%AE-2-microglobulin-independent-ligand-on-cancer-cells
#2
Lavanya Thiruchelvam-Kyle, Sigurd E Hoelsbrekken, Per C Saether, Elisabeth Gyllensten Bjørnsen, Daniela Pende, Sigbjørn Fossum, Michael R Daws, Erik Dissen
The functions of activating members of the killer cell Ig-like receptor (KIR) family are not fully understood, as the ligands for these receptors are largely unidentified. In this study, we report that KIR2DS2 reporter cells recognize a ligand expressed by cancer cell lines. All cancer targets recognized by KIR2DS2 were also recognized by KIR2DL2 and KIR2DL3 reporters. Trogocytosis of membrane proteins from the cancer targets was observed with responding reporter cells, indicating the formation of KIR2DS2 ligand-specific immunological synapses...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28137909/ndr1-dependent-regulation-of-kindlin-3-controls-high-affinity-lfa-1-binding-and-immune-synapse-organization
#3
Naoyuki Kondo, Yoshihiro Ueda, Toshiyuki Kita, Madoka Ozawa, Takashi Tomiyama, Kaneki Yasuda, Dae-Sik Lim, Tatsuo Kinashi
Antigen-specific adhesion between T cells and antigen-presenting cells (APC) during the formation of the immunological synapse (IS) is mediated by LFA-1 and ICAM-1. Herein, LFA-1/ICAM-1 interactions were measured at the single-molecule level on supported lipid bilayers. High-affinity binding was detected at low frequencies in the inner peripheral supramolecular activation cluster (SMAC) zone that contained high levels of activated Rap1 and kindlin-3. Rap1 was essential for T cell attachment, whereas deficiencies of ste20-like kinases, Mst1/Mst2 diminished high-affinity binding, and abrogated central SMAC formation with mislocalized kindlin-3 and vesicle transport regulators involved in TCR recycling/releasing machineries, resulting in impaired T-APC interactions...
January 30, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28108449/quantification-of-fibrous-spatial-point-patterns-from-single-molecule-localization-microscopy-smlm-data
#4
Ruby Peters, Marta Benthem Muñiz, Juliette Griffié, David J Williamson, George W Ashdown, Christian D Lorenz, Dylan M Owen
MOTIVATION: Unlike conventional microscopy which produces pixelated images, SMLM produces data in the form of a list of localization coordinates - a spatial point pattern (SPP). Often, such SPPs are analyzed using cluster analysis algorithms to quantify molecular clustering within, for example, the plasma membrane. While SMLM cluster analysis is now well developed, techniques for analyzing fibrous structures remain poorly explored. RESULTS: Here, we demonstrate statistical methodology, based on Ripley's K-function to quantitatively assess fibrous structures in 2D SMLM data sets...
January 19, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28100681/lfa-1-activation-in-nk-cells-and-their-subsets-influence-of-receptors-maturation-and-cytokine-stimulation
#5
Doris Urlaub, Kristine Höfer, Martha-Lena Müller, Carsten Watzl
The integrin LFA-1 is essential for efficient activation and for cytotoxicity of NK cells because it initiates the assembly of the immunological synapse and mediates firm adhesion to the target. LFA-1 is also needed to polarize the cytotoxic machinery of the NK cell toward the target cell. The binding affinity and avidity of integrins can be regulated via inside-out signals from other receptors. In this article, we investigate the signals necessary to activate LFA-1 in human NK cells. Our data show that LFA-1 has a low ligand-binding activity in resting human NK cells, but it can be stimulated by triggering activating receptors, such as 2B4 or CD16, or by coactivation of different receptor combinations...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28057175/pour-comprendre-l%C3%A2-activation-lymphocytaire-t
#6
Jeanne Galaine, Yann Godet, Olivier Adotévi
T cells activation is a finely regulated process to establish an effective anti-infectious or antitumor immune response while avoiding harmful autoimmune reactions. Although T cells are considered to be the main protagonists of the antitumor immune response, they act in interaction with other immune cells. The meeting of naive T cells with dendritic cells induces their differentiation into effector cells following the recognition of the peptide-MHC complex by the T cell receptor. The interaction of costimulatory molecules present on the surface of T cells with their ligand (s) expressed by mature dendritic cells contribute to the optimal T cell activation and to the formation of the immunological synapse...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28036020/bispecific-antibodies-as-a-development-platform-for-new-concepts-and-treatment-strategies
#7
REVIEW
Fa Yang, Weihong Wen, Weijun Qin
With the development of molecular cloning technology and the deep understanding of antibody engineering, there are diverse bispecific antibody formats from which to choose to pursue the optimal biological activity and clinical purpose. The single-chain-based bispecific antibodies usually bridge tumor cells with immune cells and form an immunological synapse because of their relatively small size. Bispecific antibodies in the IgG format include asymmetric bispecific antibodies and homodimerized bispecific antibodies, all of which have an extended blood half-life and their own crystalline fragment (Fc)-mediated functions...
December 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28004382/help-to-go-t-cells-transfer-cd40l-to-antigen-presenting-b-cells
#8
Michael L Dustin
Most immune cell communication takes place by intercellular transfer of cytokines or the contact-dependent interaction of surface receptors in immunological synapses. In this issue of the European Journal of Immunology, Gardell and Parker (Eur. J. Immunol. 2016, X, XXX-XXX) point to a new, hybrid mechanism for Th1-cell delivery of help to B cells, based on contact-dependent CD40L transfer. The transfer process and its specificity are both cell contact dependent and antigen dependent. CD40 expression is also required on the B-cell surface to capture the CD40L presented by the Th1 cell...
December 22, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27990323/impaired-functional-responses-in-follicular-lymphoma-cd8-tim-3-t-lymphocytes-following-tcr-engagement
#9
Pauline Gravelle, Catherine Do, Camille Franchet, Sabina Mueller, Lucie Oberic, Loïc Ysebaert, Luigi Maria Larocca, Stefan Hohaus, Marie-Noëlle Calmels, François-Xavier Frenois, Robert Kridel, Randy D Gascoyne, Guy Laurent, Pierre Brousset, Salvatore Valitutti, Camille Laurent
Upregulation of T cell immunoglobulin-3 (TIM-3) has been associated with negative regulation of the immune response in chronic infection and cancer, including lymphoma. Here, we investigated the possible correlation between TIM-3 expression by ex vivo cytotoxic T cells (CTL) from follicular lymphoma (FL) biopsies and their functional unresponsiveness that could limit the favorable impact of CTL on disease progression. We report a high percentage of CD8(+)TIM-3(+)T cells in lymph nodes of FL patients. When compared to their CD8(+)TIM-3(-) counterparts, CD8(+)TIM-3(+) T cells exhibited defective cytokine production following TCR engagement...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27986534/mechanical-communication-at-the-immunological-synapse
#10
REVIEW
Roshni Basu, Morgan Huse
T and B lymphocytes communicate by forming immunological synapses with antigen-presenting target cells. These highly dynamic contacts are characterized by continuous cytoskeletal remodeling events, which not only structure the interface but also exert a considerable amount of mechanical force. In recent years, it has become increasingly clear that synaptic forces influence information transfer both into and out of the lymphocyte. Here, we review our current understanding of synapse mechanics, focusing on its role as an avenue for intercellular communication...
December 13, 2016: Trends in Cell Biology
https://www.readbyqxmd.com/read/27980602/size-dependent-protein-segregation-at-membrane-interfaces
#11
Eva M Schmid, Matthew H Bakalar, Kaushik Choudhuri, Julian Weichsel, HyoungSook Ann, Phillip L Geissler, Michael L Dustin, Daniel A Fletcher
Membrane interfaces formed at cell-cell junctions are associated with characteristic patterns of membrane protein organization, such as E-cadherin enrichment in epithelial junctional complexes and CD45 exclusion from the signaling foci of immunological synapses. To isolate the role of protein size in these processes, we reconstituted membrane interfaces in vitro using giant unilamellar vesicles decorated with synthetic binding and non-binding proteins. We show that size differences between binding and non-binding proteins can dramatically alter their organization at membrane interfaces in the absence of active contributions from the cytoskeleton, with as little as a ~5 nm increase in non-binding protein size driving its exclusion from the interface...
July 2016: Nature Physics
https://www.readbyqxmd.com/read/27920282/nmda-receptor-encephalitis-and-other-antibody-mediated-disorders-of-the-synapse-the-2016-cotzias-lecture
#12
Josep Dalmau
Investigations during the last 10 years have revealed a group of disorders mediated by antibodies against ion channels and synaptic receptors, which cause both neurologic and psychiatric symptoms. In this review, I discuss the process of discovery and immunologic triggers of these disorders, and use anti-NMDA receptor encephalitis to emphasize the importance of understanding the underlying physiopathologic mechanisms in those diseases. A better knowledge of these mechanisms reveals points of convergence with other disorders (e...
December 6, 2016: Neurology
https://www.readbyqxmd.com/read/27911218/aberrant-t-cell-immunity-triggered-by-human-respiratory-syncytial-virus-and-human-metapneumovirus-infection
#13
Andrea E González, Margarita K Lay, Evelyn L Jara, Janyra A Espinoza, Roberto S Gómez, Jorge Soto, Claudia A Rivera, Katia Abarca, Susan M Bueno, Claudia A Riedel, Alexis M Kalergis
Human Respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are the two major etiological viral agents of lower respiratory tract diseases, affecting mainly infants, young children and the elderly. Although the infection of both viruses trigger an antiviral immune response that mediate viral clearance and disease resolution in immunocompetent individuals, the promotion of long-term immunity appears to be deficient and reinfection are common throughout life. A possible explanation for this phenomenon is that hRSV and hMPV, can induce aberrant T cell responses, which leads to exacerbated lung inflammation and poor T and B cell memory immunity...
December 2, 2016: Virulence
https://www.readbyqxmd.com/read/27908937/the-centrosome-a-multitalented-renaissance-organelle
#14
REVIEW
Anastassiia Vertii, Heidi Hehnly, Stephen Doxsey
The centrosome acts as a microtubule-organizing center (MTOC) from the G1 to G2 phases of the cell cycle; it can mature into a spindle pole during mitosis and/or transition into a cilium by elongating microtubules (MTs) from the basal body on cell differentiation or cell cycle arrest. New studies hint that the centrosome functions in more than MT organization. For instance, it has recently been shown that a specific substructure of the centrosome-the mother centriole appendages-are required for the recycling of endosomes back to the plasma membrane...
December 1, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27833610/tcr-triggering-induces-the-formation-of-lck-rack1-actinin-1-multiprotein-network-affecting-lck-redistribution
#15
Ondřej Ballek, Jan Valečka, Martina Dobešová, Adéla Broučková, Jasper Manning, Pavel Řehulka, Jiří Stulík, Dominik Filipp
The initiation of T-cell signaling is critically dependent on the function of the member of Src family tyrosine kinases, Lck. Upon T-cell antigen receptor (TCR) triggering, Lck kinase activity induces the nucleation of signal-transducing hubs that regulate the formation of complex signaling network and cytoskeletal rearrangement. In addition, the delivery of Lck function requires rapid and targeted membrane redistribution, but the mechanism underpinning this process is largely unknown. To gain insight into this process, we considered previously described proteins that could assist in this process via their capacity to interact with kinases and regulate their intracellular translocations...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27823906/study-of-the-t-cell-receptor-repertoire-by-cdr3-spectratyping
#16
REVIEW
Claudio Fozza, Francesca Barraqueddu, Giovanna Corda, Salvatore Contini, Patrizia Virdis, Fausto Dore, Silvana Bonfigli, Maurizio Longinotti
The T-cell receptor (TCR) is the key player within the so called immunological synapse and the analysis of its repertoire offers a picture of both versatility and wideness of the whole immune T-cell compartment. Among the different approaches applied to its study the so-called spectratyping identifies the pattern of the third complementarity determining region (CDR3) length distribution in each one of the beta variable (TRBV) subfamilies encoded by the corresponding genes. This technique consists in a CDR3 fragment analysis through capillary electrophoresis, performed after cell separation, RNA extraction and reverse transcriptase PCR...
January 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27799367/formin-generated-actomyosin-arcs-propel-t-cell-receptor-microcluster-movement-at-the-immune-synapse
#17
Sricharan Murugesan, Jinsung Hong, Jason Yi, Dong Li, Jordan R Beach, Lin Shao, John Meinhardt, Grey Madison, Xufeng Wu, Eric Betzig, John A Hammer
Actin assembly and inward flow in the plane of the immunological synapse (IS) drives the centralization of T cell receptor microclusters (TCR MCs) and the integrin leukocyte functional antigen 1 (LFA-1). Using structured-illumination microscopy (SIM), we show that actin arcs populating the medial, lamella-like region of the IS arise from linear actin filaments generated by one or more formins present at the IS distal edge. After traversing the outer, Arp2/3-generated, lamellipodia-like region of the IS, these linear filaments are organized by myosin II into antiparallel concentric arcs...
November 7, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27798165/hiv-1-nef-impairs-the-formation-of-calcium-membrane-territories-controlling-the-signaling-nanoarchitecture-at-the-immunological-synapse
#18
Joana G Silva, Nuno P Martins, Ricardo Henriques, Helena Soares
The ability of HIV-1 to replicate and to establish long-term reservoirs is strongly influenced by T cell activation. Through the use of membrane-tethered, genetically encoded calcium (Ca(2+)) indicators, we were able to detect for the first time, to our knowledge, the formation of Ca(2+) territories and determine their role in coordinating the functional signaling nanostructure of the synaptic membrane. Consequently, we report a previously unknown immune subversion mechanism involving HIV-1 exploitation, through its Nef accessory protein, of the interconnectivity among three evolutionarily conserved cellular processes: vesicle traffic, signaling compartmentalization, and the second messenger Ca(2+) We found that HIV-1 Nef specifically associates with the traffic regulators MAL and Rab11b compelling the vesicular accumulation of Lck...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27787792/analysis-of-t-cell-activation-by-confocal-microscopy
#19
Paola Larghi, Antonella Viola, Barbara Molon
Antigen-recognition by T cells requires the physical association with an antigen presenting cell (APC). At the interface between a T cell and an APC, the orchestrated redistribution of lipids, membrane receptors, and intracellular adaptors assembles a highly specialized junction, controlling the communication between the two cells, named the immunologic synapse (IS). The proper organization of the IS is a key step in host defense. Indeed, an appropriate T cell-APC interaction ensures the elimination of a wide range of pathogens and aberrant cells, whereas a deregulated IS formation leads to pathological situations such as infections, tumor development, or autoimmunity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27757297/novel-non-canonical-role-of-stat1-in-natural-killer-cell-cytotoxicity
#20
Eva Maria Putz, Andrea Majoros, Dagmar Gotthardt, Michaela Prchal-Murphy, Eva Maria Zebedin-Brandl, Daniela Alexandra Fux, Andreas Schlattl, Robert D Schreiber, Sebastian Carotta, Mathias Müller, Christopher Gerner, Thomas Decker, Veronika Sexl
STAT1 is an important regulator of NK cell maturation and cytotoxicity. Although the consequences of Stat1-deficiency have been described in detail the underlying molecular functions of STAT1 in NK cells are only partially understood. Here, we describe a novel non-canonical role of STAT1 that was unmasked in NK cells expressing a Stat1-Y701F mutant. This mutation prevents JAK-dependent phosphorylation, subsequent nuclear translocation and cytokine-induced transcriptional activity as verified by RNA-seq analysis...
2016: Oncoimmunology
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