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Immunological synapse

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https://www.readbyqxmd.com/read/27911218/aberrant-t-cell-immunity-triggered-by-human-respiratory-syncytial-virus-and-human-metapneumovirus-infection
#1
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
#2
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
#3
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
#4
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...
November 4, 2016: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27799367/formin-generated-actomyosin-arcs-propel-t-cell-receptor-microcluster-movement-at-the-immune-synapse
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/27724938/infection-with-plasmodium-berghei-ookinetes-alters-protein-expression-in-the-brain-of-anopheles-albimanus-mosquitoes
#9
Alejandro Alvarado-Delgado, Guillermo Perales Ortiz, Ángel T Tello-López, Sergio Encarnación, Renaud Conde, Ángel G Martínez-Batallar, Ken Moran-Francia, Humberto Lanz-Mendoza
BACKGROUND: The behaviour of Anopheles spp. mosquitoes, vectors for Plasmodium parasites, plays a crucial role in the propagation of malaria to humans. Consequently, it is important to understand how the behaviour of these mosquitoes is influenced by the interaction between the brain and immunological status. The nervous system is intimately linked to the immune and endocrine systems. There is evidence that the malaria parasite alters the function of these systems upon infecting the mosquito...
October 11, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27647907/optimal-activation-of-fc-mediated-effector-functions-by-influenza-virus-hemagglutinin-antibodies-requires-two-points-of-contact
#10
Paul E Leon, Wenqian He, Caitlin E Mullarkey, Mark J Bailey, Matthew S Miller, Florian Krammer, Peter Palese, Gene S Tan
Influenza virus strain-specific monoclonal antibodies (mAbs) provide protection independent of Fc gamma receptor (FcγR) engagement. In contrast, optimal in vivo protection achieved by broadly reactive mAbs requires Fc-FcγR engagement. Most strain-specific mAbs target the head domain of the viral hemagglutinin (HA), whereas broadly reactive mAbs typically recognize epitopes within the HA stalk. This observation has led to questions regarding the mechanism regulating the activation of Fc-dependent effector functions by broadly reactive antibodies...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27630246/hiv-envelope-gp120-alters-t-cell-receptor-mobilization-in-the-immunological-synapse-of-uninfected-cd4-t-cells-and-augments-t-cell-activation
#11
Jing Deng, Yu-Ya Mitsuki, Guomiao Shen, Jocelyn C Ray, Claudia Cicala, James Arthos, Michael L Dustin, Catarina E Hioe
: HIV is transmitted most efficiently from cell to cell, and productive infection occurs mainly in activated CD4 T cells. It is postulated that HIV exploits immunological synapses formed between CD4 T cells and antigen-presenting cells to facilitate the targeting and infection of activated CD4 T cells. This study sought to evaluate how the presence of the HIV envelope (Env) in the CD4 T cell immunological synapse affects synapse formation and intracellular signaling to impact the downstream T cell activation events...
December 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27622064/loss-of-dnam-1-ligand-expression-by-acute-myeloid-leukemia-cells-renders-them-resistant-to-nk-cell-killing
#12
Conor J Kearney, Kelly M Ramsbottom, Ilia Voskoboinik, Phillip K Darcy, Jane Oliaro
Acute myeloid leukemia (AML) is associated with poor natural killer (NK) cell function through aberrant expression of NK-cell-activating receptors and their ligands on tumor cells. These alterations are thought to promote formation of inhibitory NK-target cell synapses, in which killer cell degranulation is attenuated. Allogeneic stem cell transplantation can be effective in treating AML, through restoration of NK cell lytic activity. Similarly, agents that augment NK-cell-activating signals within the immunological synapse may provide some therapeutic benefit...
August 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27613223/downstream-effect-profiles-discern-different-mechanisms-of-integrin-%C3%AE-l%C3%AE-2-inhibition
#13
Riccardo V Mancuso, Karl Welzenbach, Peter Steinberger, Stephan Krähenbühl, Gabriele Weitz-Schmidt
The integrin leucocyte function-associated antigen-1 (αLβ2, LFA-1) plays crucial roles in T cell adhesion, migration and immunological synapse (IS) formation. Consequently, αLβ2 is an important therapeutic target in autoimmunity. Three major classes of αLβ2 inhibitors with distinct modes of action have been described to date: Monoclonal antibodies (mAbs), small molecule α/β I allosteric and small molecule α I allosteric inhibitors. The objective of this study was to systematically compare these three modes of αLβ2 inhibition for their αLβ2 inhibitory as well as their potential agonist-like effects...
November 1, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27585956/preparing-the-lethal-hit-interplay-between-exo-and-endocytic-pathways-in-cytotoxic-t-lymphocytes
#14
Hsin-Fang Chang, Hawraa Bzeih, Praneeth Chitirala, Keerthana Ravichandran, Marwa Sleiman, Elmar Krause, Ulrike Hahn, Varsha Pattu, Jens Rettig
Cytotoxic T lymphocytes patrol our body in search for infected cells which they kill through the release of cytotoxic substances contained in cytotoxic granules. The fusion of cytotoxic granules occurs at a specially formed contact site, the immunological synapse, and is tightly controlled to ensure specificity. In this review, we discuss the contribution of two intracellular compartments, endosomes and cytotoxic granules, to the formation, function and disassembly of the immunological synapse. We highlight a recently proposed sequential process of fusion events at the IS upon target cell recognition...
September 1, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27560832/histamine-regulates-murine-primary-dendritic-cell-functions
#15
Heiko Schenk, Detlef Neumann, Christina Kloth
OBJECTIVE AND DESIGN: The modulation of antigen uptake and activation of dendritic cells (DCs) by histamine may function as a regulator of inflammation. Therefore, we sought to determine the impact of histamine on antigen uptake by and activation of murine DCs. MATERIAL AND METHODS: DCs from spleen and lung were either identified by flow cytometry or were immunomagnetically enriched. Cells were stimulated with histamine, and the regulation of MHC-II and co-stimulatory molecule expression (CD80, CD86, and ICOS-L) and antigen uptake were quantified by flow cytometry...
October 2016: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/27534551/dynein-separately-partners-with-nde1-and-dynactin-to-orchestrate-t-cell-focused-secretion
#16
Shubhankar Nath, Laura Christian, Sarah Youngsun Tan, Sanghee Ki, Lauren I R Ehrlich, Martin Poenie
Helper and cytotoxic T cells accomplish focused secretion through the movement of vesicles toward the microtubule organizing center (MTOC) and translocation of the MTOC to the target contact site. In this study, using Jurkat cells and OT-I TCR transgenic primary murine CTLs, we show that the dynein-binding proteins nuclear distribution E homolog 1 (NDE1) and dynactin (as represented by p150(Glued)) form mutually exclusive complexes with dynein, exhibit nonoverlapping distributions in target-stimulated cells, and mediate different transport events...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27533792/the-functional-interplay-of-rab11-fip3-and-rho-proteins-on-the-endosomal-recycling-pathway-controls-cell-shape-and-symmetry
#17
Jérôme Bouchet, Mary W McCaffrey, Andrea Graziani, Andrés Alcover
Several families of small GTPases regulate a variety of fundamental cellular processes, encompassing growth factor signal transduction, vesicular trafficking and control of the cytoskeleton. Frequently, their action is hierarchical and complementary, but much of the detail of their functional interactions remains to be clarified. It is well established that Rab family members regulate a variety of intracellular vesicle trafficking pathways. Moreover, Rho family GTPases are pivotal for the control of the actin and microtubule cytoskeleton...
August 17, 2016: Small GTPases
https://www.readbyqxmd.com/read/27503907/increased-ex-vivo-antigen-presentation-profile-of-b-cells-in-multiple-sclerosis
#18
Amandine Mathias, Guillaume Perriard, Mathieu Canales, Charlotte Soneson, Mauro Delorenzi, Myriam Schluep, Renaud A Du Pasquier
BACKGROUND: Multiple sclerosis (MS) is thought to be T cell mediated but the mechanisms eliciting such a dysregulated adaptative immune response remain enigmatic. OBJECTIVE: To examine the activation profile of antigen-presenting cells (APCs) in MS. METHODS: A total of 98 study subjects were enrolled including patients suffering from relapsing-remitting, secondary- and primary-progressive (PP) MS, other inflammatory neurological diseases, and healthy controls...
August 8, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/27501450/signaling-and-polarized-communication-across-the-t-cell-immunological-synapse
#19
Michael L Dustin, Kaushik Choudhuri
T cells express a somatically recombined antigen receptor (αβTCR) that is calibrated during development to respond to changes in peptides displayed by major histocompatibility complex proteins (pMHC) on the surface of antigen-presenting cells (APC). A key characteristic of pMHC for adaptive immunity is the ability to sample internal states of cells and tissues to sensitively detect changes associated with infection, cell derangement, or tissue injury. Physical T cell-APC contact sets up an axis for polarization of TCR, adhesion molecules, kinases, cytoskeletal elements, and organelles inherent in this mode of juxtacrine signaling...
October 6, 2016: Annual Review of Cell and Developmental Biology
https://www.readbyqxmd.com/read/27477328/immune-dysregulation-in-patients-with-pten-hamartoma-tumor-syndrome-analysis-of-foxp3-regulatory-t%C3%A2-cells
#20
Hannah H Chen, Norman Händel, Joanne Ngeow, James Muller, Michael Hühn, Huei-Ting Yang, Mario Heindl, Roos-Marijn Berbers, Ahmed N Hegazy, Janina Kionke, Lamis Yehia, Ulrich Sack, Frank Bläser, Anne Rensing-Ehl, Julia Reifenberger, Julia Keith, Simon Travis, Andreas Merkenschlager, Wieland Kiess, Christian Wittekind, Lisa Walker, Stephan Ehl, Stefan Aretz, Michael L Dustin, Charis Eng, Fiona Powrie, Holm H Uhlig
BACKGROUND: Patients with heterozygous germline mutations in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) experience autoimmunity and lymphoid hyperplasia. OBJECTIVES: Because regulation of the phosphoinositide 3-kinase (PI3K) pathway is critical for maintaining regulatory T (Treg) cell functions, we investigate Treg cells in patients with heterozygous germline PTEN mutations (PTEN hamartoma tumor syndrome [PHTS]). METHODS: Patients with PHTS were assessed for immunologic conditions, lymphocyte subsets, forkhead box P3 (FOXP3)(+) Treg cell levels, and phenotype...
June 18, 2016: Journal of Allergy and Clinical Immunology
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