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Immunological synapse

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
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
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
Jing Deng, Yu-Ya Mitsuki, Guomiao Shen, Jocelyn 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...
September 14, 2016: Journal of Virology
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
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
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
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
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
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
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
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
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
Benjamin Rengstl, Frederike Schmid, Christian Weiser, Claudia Döring, Tim Heinrich, Kathrin Warner, Petra S A Becker, Robin Wistinghausen, Sima Kameh-Var, Eva Werling, Arne Billmeier, Christian Seidl, Sylvia Hartmann, Hinrich Abken, Ralf Küppers, Martin-Leo Hansmann, Sebastian Newrzela
Hodgkin lymphoma (HL) presents with a unique histologic pattern. Pathognomonic Hodgkin and Reed-Sternberg (HRS) cells usually account for less than 1% of the tumor and are embedded in a reactive infiltrate mainly comprised of CD4(+) T cells. HRS cells induce an immunosuppressive microenvironment and thereby escape antitumor immunity. To investigate the impact of interactions between HRS cells and T cells, we performed long-term co-culture studies that were further translated into a xenograft model. Surprisingly, we revealed a strong antitumor potential of allogeneic CD4(+) T cells against HL cell lines...
June 2016: Oncoimmunology
Ilaria Maccari, Renping Zhao, Martin Peglow, Karsten Schwarz, Ivan Hornak, Mathias Pasche, Ariel Quintana, Markus Hoth, Bin Qu, Heiko Rieger
Ca(2+) microdomains and spatially resolved Ca(2+) signals are highly relevant for cell function. In T cells, local Ca(2+) signaling at the immunological synapse (IS) is required for downstream effector functions. We present experimental evidence that the relocation of the MTOC towards the IS during polarization drags mitochondria along with the microtubule network. From time-lapse fluorescence microscopy we conclude that mitochondria rotate together with the cytoskeleton towards the IS. We hypothesize that this movement of mitochondria towards the IS together with their functionality of absorption and spatial redistribution of Ca(2+) is sufficient to significantly increase the cytosolic Ca(2+) concentration...
July 7, 2016: Cell Calcium
Akiko Hashimoto-Tane, Takashi Saito
The interaction between a T cell and an antigen-presenting cell is the initiating event in T cell-mediated adaptive immunity. The Immunological Synapse (IS) is formed at the interface between these two cell types, and is the site where antigen (Ag)-specific recognition and activation are induced through the T cell receptor (TCR). This occurs at the center of the IS, and cell adhesion is supported through integrins in the area surrounding the TCR. Recently, this model has been revised based on data indicating that the initial Ag-specific activation signal is triggered prior to IS formation at TCR-microclusters (MCs), sites where TCR, kinases and adaptors of TCR proximal downstream signaling molecules accumulate as an activation signaling cluster...
2016: Frontiers in Immunology
Karla K Frietze, Adlai L Pappy, Jack W Melson, Emily E O'Driscoll, Carolyn M Tyler, David H Perlman, Lisa M Boulanger
BACKGROUND: Major histocompatibility complex class I (MHCI) proteins present antigenic peptides for immune surveillance and play critical roles in nervous system development and plasticity. Most MHCI are transmembrane proteins. The extracellular domain of MHCI interacts with immunoreceptors, peptides, and co-receptors to mediate immune signaling. While the cytoplasmic domain also plays important roles in endocytic trafficking, cross-presentation of extracellularly derived antigens, and CTL priming, the molecular mediators of cytoplasmic signaling by MHCI remain largely unknown...
2016: BMC Immunology
Nadiv Dharan, Oded Farago
Cell-cell adhesion is established by specific binding of receptor and ligand proteins anchored in the cell membranes. The adhesion bonds attract each other and often aggregate into large clusters that are central to many biological processes. One possible origin of attractive interactions between adhesion bonds is the elastic response of the membranes to their deformation by the bonds. Here, we analyze these elasticity-mediated interactions using a novel mean-field approach. Our analysis of systems at different densities of bonds, ϕ, reveals that the phase diagram, i...
August 21, 2016: Soft Matter
Guillermo Ramírez-Santiago, Javier Robles-Valero, Giulia Morlino, Aranzazu Cruz-Adalia, Manuel Pérez-Martínez, Airen Zaldivar, Mónica Torres-Torresano, Francisco Javier Chichón, Andrea Sorrentino, Eva Pereiro, José L Carrascosa, Diego Megías, Carlos Oscar S Sorzano, Francisco Sánchez-Madrid, Esteban Veiga
Lymphocyte migration, which is essential for effective immune responses, belongs to the so-called amoeboid migration. The lymphocyte migration is up to 100 times faster than between mesenchymal and epithelial cell types. Migrating lymphocytes are highly polarized in three well-defined structural and functional zones: uropod, medial zone and leading edge. The actiomyosin-dependent driving force moves forward the uropod, whereas massive actin rearrangements protruding the cell membrane are observed at the leading edge...
July 13, 2016: European Journal of Immunology
Marianne Strazza, Inbar Azoulay-Alfaguter, Michael Peled, Adam Mor
Overall, T cell adhesion is a critical component of function, contributing to the distinct processes of cellular recruitment to sites of inflammation and interaction with antigen presenting cells (APC) in the formation of immunological synapses. These two contexts of T cell adhesion differ in that T cell-APC interactions can be considered static, while T cell-blood vessel interactions are challenged by the shear stress generated by circulation itself. T cell-APC interactions are classified as static in that the two cellular partners are static relative to each other...
2016: Journal of Visualized Experiments: JoVE
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