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Immunological synapse

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https://www.readbyqxmd.com/read/30416506/expanding-the-therapeutic-window-for-car-t-cell-therapy-in-solid-tumors-the-knowns-and-unknowns-of-car-t-cell-biology
#1
REVIEW
Keisuke Watanabe, Shunichiro Kuramitsu, Avery D Posey, Carl H June
A major obstacle for chimeric antigen receptor (CAR) T cell therapy in solid tumors is the lack of truly tumor-specific target antigens, which translates to the targeting of tumor-associated antigens (TAAs) overexpressed on tumors but shared with normal organs, raising safety concerns. In addition, expression of TAAs in solid tumors is particularly heterogeneous. In this regard, it is critical to deeply understand the sensitivity of CAR T cells, especially against low-density targets and the possible therapeutic window of antigen density targeted by CAR T cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30408601/characterisation-of-amphioxus-protein-kinase-c-%C3%AE-%C3%AE-reveals-a-unique-proto-v3-domain-suggesting-an-evolutionary-mechanism-for-pkc-%C3%AE-unique-v3
#2
Zhi-Long Chen, Bei-Ni Gong, Qi-Long Wang, Zhi-Hui Xiao, Chong Deng, Wen-Qian Wang, Yingqiu Li
A primitive adaptive immune system has recently been suggested to be present in a basal chordate amphioxus (Branchiostoma belcheri, Bb), making it an ideal model for studying the origin of adaptive immune. The novel protein kinase C isoform PKC-θ, but not its closest isoform PKC-δ, plays a critical role for mammalian T-cell activation via translocation to immunological synapse (IS) mediated by a unique PKC-θ V3 domain containing one PxxP motif. To understand the evolution of this unique PKC-θ V3 domain and the primitive adaptive immune system in amphioxus, we comparatively studied the orthologs of PKC-δ and -θ from amphioxus and other species...
November 5, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/30388704/galectin-3-regulates-%C3%AE-herpesvirus-specific-cd8-t-cell-immunity
#3
Manpreet Kaur, Dhaneshwar Kumar, Vincent Butty, Sudhakar Singh, Alexandre Esteban, Gerald R Fink, Hidde L Ploegh, Sharvan Sehrawat
To gain insights into the molecular mechanisms and pathways involved in the activation of γ-herpesvirus (MHV68)-specific T cell receptor transnuclear (TN) CD8+ T cells, we performed a comprehensive transcriptomic analysis. Upon viral infection, we observed differential expression of several thousand transcripts encompassing various networks and pathways in activated TN cells compared with their naive counterparts. Activated cells highly upregulated galectin-3. We therefore explored the role of galectin-3 in influencing anti-MHV68 immunity...
October 17, 2018: iScience
https://www.readbyqxmd.com/read/30366518/tumor-necrosis-factor-receptor-superfamily-in-t-cell-priming-and-effector-function
#4
James Muller, Audrey Baeyens, Michael L Dustin
The tumor necrosis factor receptor superfamily (TNFRSF) and their ligands mediate lymphoid tissue development and homeostasis in addition to key aspects of innate and adaptive immune responses. T cells of the adaptive immune system express a number of TNFRSF members that are used to receive signals at different instructive stages and produce several tumor necrosis factor superfamily (TNFSF) members as effector molecules. There is also one example of a TNFRSF member serving as a ligand for negative regulatory checkpoint receptors...
2018: Advances in Immunology
https://www.readbyqxmd.com/read/30356797/biophysical-characterization-of-cd6-tcr-cd3-interplay-in-t-cells
#5
Marjolein B M Meddens, Svenja F B Mennens, F Burcu Celikkol, Joost Te Riet, Johannes S Kanger, Ben Joosten, J Joris Witsenburg, Roland Brock, Carl G Figdor, Alessandra Cambi
Activation of the T cell receptor (TCR) on the T cell through ligation with antigen-MHC complex of an antigen-presenting cell (APC) is an essential process in the activation of T cells and induction of the subsequent adaptive immune response. Upon activation, the TCR, together with its associated co-receptor CD3 complex, assembles in signaling microclusters that are transported to the center of the organizational structure at the T cell-APC interface termed the immunological synapse (IS). During IS formation, local cell surface receptors and associated intracellular molecules are reorganized, ultimately creating the typical bull's eye-shaped pattern of the IS...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30344520/the-role-of-the-immunological-synapse-in-differential-effects-of-apc-subsets-in-alloimmunization-to-fresh-non-stored-rbcs
#6
Amanda L Richards, Kathryn Sheldon, Xiaoping Wu, David R Gruber, Krystalyn E Hudson
Background: Each year, over 5 million red blood cell (RBC) transfusions are administered to patients in the USA. Despite the therapeutic benefits of RBC transfusions, there are associated risks. RBC-specific alloantibodies may form in response to antigenic differences between RBC donors and recipients; these alloantibodies can be a problem as they may mediate hemolysis or pose barriers to future transfusion support. While there is currently no reliable way to predict which RBC recipients will make an alloantibody response, risk factors such as inflammation have been shown to correlate with increased rates of RBC alloimmunization...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30339020/two-dimensional-label-free-affinity-analysis-of-tumor-specific-cd8-t-cells-with-a-biomimetic-plasmonic-sensor
#7
Maria Soler, Xiaokang Li, Aurelian John-Herpin, Julien Schmidt, George Coukos, Hatice Altug
The screening and analysis of T cells functional avidity for specific tumor-associated antigens is crucial for the development of personalized immunotherapies against cancer. The affinity and kinetics of a T cell receptor (TCR) binding to the peptide-major histocompatibility complex (pMHC), expressed on tumor or antigen-presenting cells, have shown major implications in T cell activation and effector functions. We introduce an innovative methodology for the two-dimensional affinity analysis of TCR-pMHC in a label-free configuration by employing a multiparametric Surface Plasmon Resonance biosensor (MP-SPR) functionalized with artificial cell membranes...
October 19, 2018: ACS Sensors
https://www.readbyqxmd.com/read/30327650/hcmv-encoded-nk-modulators-lessons-from-in-vitro-and-in-vivo-genetic-variation
#8
REVIEW
Mihil Patel, Virginia-Maria Vlahava, Simone K Forbes, Ceri A Fielding, Richard J Stanton, Eddie C Y Wang
Human cytomegalovirus (HCMV) is under constant selective pressure from the immune system in vivo . Study of HCMV genes that have been lost in the absence of, or genetically altered by, such selection can focus research toward findings of in vivo significance. We have been particularly interested in the most pronounced change in the highly passaged laboratory strains AD169 and Towne-the deletion of 13-15 kb of sequence (designated the UL /b' region) that encodes up to 22 canonical genes, UL133-UL150. At least 5 genes have been identified in UL /b' that inhibit NK cell function...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30319617/membrane-ultrastructure-and-t-cell-activation
#9
REVIEW
Johannes Pettmann, Ana Mafalda Santos, Omer Dushek, Simon J Davis
The immune system serves as a crucial line of defense from infection and cancer, while also contributing to tissue homeostasis. Communication between immune cells is mediated by small soluble factors called cytokines, and also by direct cellular interactions. Cell-cell interactions are particularly important for T cell activation. T cells direct the adaptive immune response and therefore need to distinguish between self and foreign antigens. Even though decades have passed since the discovery of T cells, exactly why and how they are able to recognize and discriminate between antigens is still not fully understood...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30287618/an-autoimmune-disease-variant-of-igg1-modulates-b-cell-activation-and-differentiation
#10
Xiangjun Chen, Xiaolin Sun, Wei Yang, Bing Yang, Xiaozhen Zhao, Shuting Chen, Lili He, Hui Chen, Changmei Yang, Le Xiao, Zai Chang, Jianping Guo, Jing He, Fuping Zhang, Fang Zheng, Zhibin Hu, Zhiyong Yang, Jizhong Lou, Wenjie Zheng, Hai Qi, Chenqi Xu, Hong Zhang, Hongying Shan, Xujie Zhou, Qingwen Wang, Yi Shi, Luhua Lai, Zhanguo Li, Wanli Liu
The maintenance of autoreactive B cells in a quiescent state is crucial for preventing autoimmunity. Here, we identify a variant of human IgG1 (hIgG1-G396R), which positively correlates with systemic lupus erythematosus. In induced lupus models, murine homolog G390R knock-in mice generate excessive numbers of plasma cells, leading to a burst of broad-spectrum autoantibodies. This enhanced production of antibodies is also observed in hapten-immunized G390R mice, as well as in influenza-vaccinated human G396R homozygous carriers...
October 4, 2018: Science
https://www.readbyqxmd.com/read/30283780/the-actin-cytoskeleton-a-mechanical-intermediate-for-signal-integration-at-the-immunological-synapse
#11
Nathan H Roy, Janis K Burkhardt
The immunological synapse (IS) is a specialized structure that serves as a platform for cell-cell communication between a T cell and an antigen-presenting cell (APC). Engagement of the T cell receptor (TCR) with cognate peptide-MHC complexes on the APC activates the T cell and instructs its differentiation. Proper T cell activation also requires engagement of additional receptor-ligand pairs, which promote sustained adhesion and deliver costimulatory signals. These events are orchestrated by T cell actin dynamics, which organize IS components and facilitate their signaling...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/30283450/commentary-integrins-modulate-t-cell-receptor-signaling-by-constraining-actin-flow-at-the-immunological-synapse
#12
COMMENT
Aviad Ben-Shmuel, Noah Joseph, Mira Barda-Saad
No abstract text is available yet for this article.
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30282749/hiv-1-nef-hijacks-lck-and-rac1-endosomal-traffic-to-dually-modulate-signaling-mediated-and-actin-cytoskeleton-mediated-t-cell-functions
#13
Iratxe Del Río-Iñiguez, Elena Vázquez-Chávez, Céline Cuche, Vincenzo Di Bartolo, Jérôme Bouchet, Andrés Alcover
Endosomal traffic of TCR and signaling molecules regulates immunological synapse formation and T cell activation. We recently showed that Rab11 endosomes regulate the subcellular localization of the tyrosine kinase Lck and of the GTPase Rac1 and control their functions in TCR signaling and actin cytoskeleton remodeling. HIV-1 infection of T cells alters their endosomal traffic, activation capacity, and actin cytoskeleton organization. The viral protein Nef is pivotal for these modifications. We hypothesized that HIV-1 Nef could jointly alter Lck and Rac1 endosomal traffic and concomitantly modulate their functions...
November 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30275048/ef-hand-domain-family-member-d2-is-required-for-t-cell-cytotoxicity
#14
Michael Peled, Matthew A Dragovich, Kieran Adam, Marianne Strazza, Anna S Tocheva, Irving E Vega, Adam Mor
Programmed cell death 1 (PD-1) is a major coinhibitory receptor and a member of the immunological synapse (IS). To uncover proteins that regulate PD-1 recruitment to the IS, we searched for cytoskeleton-related proteins that also interact with PD-1 using affinity purification mass spectrometry. Among these proteins, EF hand domain family member D2 (EFHD2), a calcium binding adaptor protein, was functionally and mechanistically analyzed for its contribution to PD-1 signaling. EFHD2 was required for PD-1 to inhibit cytokine secretion, proliferation, and adhesion of human T cells...
November 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30254128/t-cell-defects-in-patients-with-arpc1b-germline-mutations-account-for-their-combined-immunodeficiency
#15
Immacolata Brigida, Matteo Zoccolillo, Maria Pia Cicalese, Laurène Pfajfer, Federica Barzaghi, Serena Scala, Carmen Oleaga-Quintas, Jesus A Álvarez-Álvarez, Lucia Sereni, Stefania Giannelli, Claudia Sartirana, Francesca Dionisio, Luca Pavesi, Marta Benavides-Nieto, Luca Basso-Ricci, Paola Capasso, Benedetta Mazzi, Jeremie Rosain, Nufar Marcus, Yu Nee Lee, Raz Somech, Massimo Degano, Giuseppe Raiola, Roberta Caorsi, Paolo Picco, Marcela Moncada Velez, Joelle Khourieh, Andrés Augusto Arias, Aziz Bousfiha, Thomas Issekutz, Andrew Issekutz, Bertrand Boisson, Kerry Dobbs, Anna Villa, Angelo Lombardo, Benedicte Neven, Despina Moshous, Jean-Laurent Casanova, José Luis Franco, Luigi D Notarangelo, Cristina Scielzo, Stefano Volpi, Loïc Dupré, Jacinta Bustamante, Marco Gattorno, Alessandro Aiuti
ARPC1B is a key factor for the assembly and maintenance of the ARP2/3 complex that is involved in actin branching from an existing filament. Germline bi-allelic mutations in ARPC1B have been recently described in six patients with clinical features of combined immunodeficiency, whose neutrophils and platelets but not T lymphocytes were studied. We hypothesized that ARPC1B-deficiency may also lead to cytoskeleton and functional defects in T cells. We have identified bi-allelic mutations in ARPC1B in six unrelated patients with early-onset disease characterized by severe infections, autoimmune manifestations and thrombocytopenia...
September 25, 2018: Blood
https://www.readbyqxmd.com/read/30251665/revealing-the-atomistic-details-behind-the-binding-of-b7-1-to-cd28-and-ctla-4-a-comprehensive-protein-protein-modelling-study
#16
Aravindhan Ganesan, Tae Chul Moon, Khaled H Barakat
BACKGROUND: CD28 and CTLA-4 are homologous T-cell receptors that bind with B7-1 and produce two opposing immunological signals required for T-cell activation and inactivation, respectively. It has been clinically proven that specific blockade of these key protein-protein interactions at the synapse can offer immunotherapeutic benefits for cancers and autoimmune treatments. Hence, there is a growing interest towards developing anti-CD28 and anti-CTLA-4 small molecule inhibitors. To achieve this goal, it is important to understand unique molecular level fingerprint interactions that stabilize CTLA-4/B7-1 and CD28/B7-1 complexes...
August 10, 2018: Biochimica et biophysica acta. General subjects
https://www.readbyqxmd.com/read/30232280/imbalance-of-immunological-synapse-kinapse-states-reflects-tumor-escape-to-immunity-in-glioblastoma
#17
Laura R Díaz, Elena Saavedra-López, Leire Romarate, Izaskun Mitxitorena, Paola V Casanova, George P Cribaro, José M Gallego, Ana Pérez-Vallés, Jerónimo Forteza-Vila, Clara Alfaro-Cervello, José M García-Verdugo, Carlos Barcia, Carlos Barcia
Since the proper activation of T cells requires the physical interaction with target cells through the formation of immunological synapses (IS), an alteration at this level could be a reason why tumors escape the immune response. As part of their life cycle, it is thought that T cells alternate between a static phase, the IS, and a dynamic phase, the immunological kinapse (IK), depending on high or low antigen sensing. Our investigation performed in tissue samples of human glioma shows that T cells are able to establish synapsing interactions not only with glioma tumorigenic cells, but also with stromal myeloid cells...
September 20, 2018: JCI Insight
https://www.readbyqxmd.com/read/30190583/polarity-of-cd4-t-cells-towards-the-antigen-presenting-cell-is-regulated-by-the-lck-adapter-tsad
#18
Greger Abrahamsen, Vibeke Sundvold-Gjerstad, Meseret Habtamu, Bjarne Bogen, Anne Spurkland
Polarization of T cells towards the antigen presenting cell (APC) is critically important for appropriate activation and differentiation of the naïve T cell. Here we used imaging flow cytometry (IFC) and show that the activation induced Lck and Itk adapter T cell specific adapter protein (TSAd), encoded by SH2D2A, modulates polarization of T cells towards the APC. Upon exposure to APC presenting the cognate antigen Id, Sh2d2a-/- CD4+ T cells expressing Id-specific transgenic T cell receptor (TCR), displayed impaired polarization of F-actin and TCR to the immunological synapse (IS)...
September 6, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30175639/the-application-of-kisser-probes-for-resolving-the-distribution-and-microenvironment-of-membrane-proteins-in-situ
#19
Michal Stawarski, Karlis Anthony Justs, Roberto Xander Hernandez, Gregory Talisker Macleod
Membrane proteins play a lead role in the formation and function of synapses, but, despite revolutions in immunology and molecular genetics, limitations persist in our ability to investigate membrane proteins in the context of an intact synapse. Here, we introduce a simple but novel approach to resolving the distribution of endogenous membrane proteins in either live or fixed tissues. The technique involves transgenic expression of a protein with an extracellular tag, a generic transmembrane domain, and an intracellular terminus that mimics the intracellular anchoring motifs of the endogenous protein of interest...
September 3, 2018: Journal of Neurogenetics
https://www.readbyqxmd.com/read/30150988/synaptic-interactions-in-germinal-centers
#20
REVIEW
Ilenia Papa, Carola G Vinuesa
The germinal center (GC) is a complex, highly dynamic microanatomical niche that allows the generation of high-affinity antibody-producing plasma cells and memory B cells. These cells constitute the basis of long-lived highly protective antibody responses. For affinity maturation to occur, B cells undergo multiple rounds of proliferation and mutation of the genes that encode the immunoglobulin V region followed by selection by specialized T cells called follicular helper T (TFH ) cells. In order to achieve this result, the GC requires spatially and temporally coordinated interactions between the different cell types, including B and T lymphocytes and follicular dendritic cells...
2018: Frontiers in Immunology
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