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Immunological synapse

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https://www.readbyqxmd.com/read/29320731/durable-interactions-of-t-cells-with-t-cell-receptor-stimuli-in-the-absence-of-a-stable-immunological-synapse
#1
Viveka Mayya, Edward Judokusumo, Enas Abu Shah, Christopher G Peel, Willie Neiswanger, David Depoil, David A Blair, Chris H Wiggins, Lance C Kam, Michael L Dustin
T cells engage in two modes of interaction with antigen-presenting surfaces: stable synapses and motile kinapses. Although it is surmised that durable interactions of T cells with antigen-presenting cells involve synapses, in situ 3D imaging cannot resolve the mode of interaction. We have established in vitro 2D platforms and quantitative metrics to determine cell-intrinsic modes of interaction when T cells are faced with spatially continuous or restricted stimulation. All major resting human T cell subsets, except memory CD8 T cells, spend more time in the kinapse mode on continuous stimulatory surfaces...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29288201/murine-red-blood-cells-lack-ligands-for-b-cell-siglecs-allowing-strong-activation-by-erythrocyte-surface-antigens
#2
Fernando Spiller, Corwin M Nycholat, Chika Kikuchi, James C Paulson, Matthew S Macauley
CD22 and sialic acid-binding Ig-like lectin (Siglec)-G are members of the Siglec family of inhibitory coreceptors expressed on B cells that participate in enforcement of peripheral B cell tolerance. We have shown previously that when a BCR engages its cognate Ag on a cell surface that also expresses Siglec ligands, B cell Siglecs are recruited to the immunological synapse, resulting in suppression of BCR signaling and B cell apoptosis. Because all cells display sialic acids, and CD22 and Siglec-G have distinct, yet overlapping, specificities for sialic acid-containing glycan ligands, any cell could, in principle, invoke this tolerogenic mechanism for cell surface Ags...
December 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29288152/cytotoxic-granule-endocytosis-depends-on-the-flower-protein
#3
Hsin-Fang Chang, Stefanie Mannebach, Andreas Beck, Keerthana Ravichandran, Elmar Krause, Katja Frohnweiler, Claudia Fecher-Trost, Claudia Schirra, Varsha Pattu, Veit Flockerzi, Jens Rettig
Cytotoxic T lymphocytes (CTLs) kill target cells by the regulated release of cytotoxic substances from granules at the immunological synapse. To kill multiple target cells, CTLs use endocytosis of membrane components of cytotoxic granules. We studied the potential calcium dependence of endocytosis in mouse CTLs on Flower, which mediates the calcium dependence of synaptic vesicle endocytosis in Drosophila melanogaster Flower is predominantly localized on intracellular vesicles that move to the synapse on target cell contact...
December 29, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29245925/histopathological-expression-analysis-of-intercellular-adhesion-molecule-1-icam-1-along-development-and-progression-of-human-melanoma
#4
Gilli Galore-Haskel, Erez N Baruch, Amy L Berg, Iris Barshack, Itzhak Zilinsky, Camila Avivi, Michal J Besser, Jacob Schachter, Gal Markel
Intercellular adhesion molecule 1 (ICAM-1) protein is an important adhesion molecule that facilitates metastasis on one hand, and on the other hand supports the immunological synapse necessary for T-cell mediated elimination. The expression pattern of ICAM-1 in melanoma was studied more than two decades ago, mainly in cell lines or in unmatched melanoma specimens. By using real time PCR we could not demonstrate a clear difference in ICAM-1 mRNA levels between primary melanocytes and primary cultures of metastatic melanoma...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29244882/%C3%AE-ii-spectrin-in-t-cells-is-involved-in-the-regulation-of-cell-cell-contact-leading-to-immunological-synapse-formation
#5
Justyna M Meissner, Aleksander F Sikorski, Tomasz Nawara, Jakub Grzesiak, Krzysztof Marycz, Dżamila M Bogusławska, Izabela Michalczyk, Marie-Christine Lecomte, Beata Machnicka
T-lymphocyte activation after antigen presentation to the T-Cell Receptor (TCR) is a critical step in the development of proper immune responses to infection and inflammation. This dynamic process involves reorganization of the actin cytoskeleton and signaling molecules at the cell membrane, leading to the formation of the Immunological Synapse (IS). The mechanisms regulating the formation of the IS are not completely understood. Nonerythroid spectrin is a membrane skeletal protein involved in the regulation of many cellular processes, including cell adhesion, signaling and actin cytoskeleton remodeling...
2017: PloS One
https://www.readbyqxmd.com/read/29241728/an-actin-cytoskeletal-barrier-inhibits-lytic-granule-release-from-natural-killer-cells-in-chediak-higashi-syndrome
#6
Aleksandra Gil-Krzewska, Mezida B Saeed, Anna Oszmiana, Elizabeth R Fischer, Kathryn Lagrue, William A Gahl, Wendy J Introne, John E Coligan, Daniel M Davis, Konrad Krzewski
BACKGROUND: Chediak-Higashi syndrome (CHS) is a rare disorder caused by biallelic mutations in the LYST gene, resulting in formation of giant lysosomes or lysosome-related organelles in several cell types. The disease is characterized by immunodeficiency and a fatal hemophagocytic lymphohistiocytosis due to impaired function of cytotoxic lymphocytes, mainly Natural Killer (NK) cells. OBJECTIVE: We sought to determine the underlying biochemical cause of the impaired cytotoxicity of NK cells in CHS...
December 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29232699/cxcr4-blockade-decreases-cd4-t-cell-exhaustion-and-improves-survival-in-a-murine-model-of-polymicrobial-sepsis
#7
Kimberly M Ramonell, Wenxiao Zhang, Annette Hadley, Ching-Wen Chen, Katherine T Fay, John D Lyons, Nathan J Klingensmith, Kevin W McConnell, Craig M Coopersmith, Mandy L Ford
Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis...
2017: PloS One
https://www.readbyqxmd.com/read/29212907/role-of-the-ehd-family-of-endocytic-recycling-regulators-for-tcr-recycling-and-t-cell-function
#8
Fany M Iseka, Benjamin T Goetz, Insha Mushtaq, Wei An, Luke R Cypher, Timothy A Bielecki, Eric C Tom, Priyanka Arya, Sohinee Bhattacharyya, Matthew D Storck, Craig L Semerad, James E Talmadge, R Lee Mosley, Vimla Band, Hamid Band
T cells use the endocytic pathway for key cell biological functions, including receptor turnover and maintenance of the immunological synapse. Some of the established players include the Rab GTPases, the SNARE complex proteins, and others, which function together with EPS-15 homology domain-containing (EHD) proteins in non-T cell systems. To date, the role of the EHD protein family in T cell function remains unexplored. We generated conditional EHD1/3/4 knockout mice using CD4-Cre and crossed these with mice bearing a myelin oligodendrocyte glycoprotein-specific TCR transgene...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29211935/a-simple-twist-of-phosphate-immunological-synapse-formation-and-t-cell-receptor-signaling-outcome-in-regulatory-t-cells
#9
Talal A Chatila, Raffaele De Palma
Signaling through the T cell receptor (TCR) regulates T cell homeostasis and effector functions. However, a full accounting of the TCR-coupled signaling networks and how their interplay determines specific functional outcomes remains elusive. Of particular interest are efforts over the last years to elucidate distinctive features of TCR signaling in regulatory T cells (Treg) that may account for some of their unique functional attributes as compared to conventional T (Tconv) cells. In this issue of the European Journal of Immunology, van Ham et al...
December 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29186690/growth-of-b-cell-receptor-microclusters-is-regulated-by-pip2-and-pip3-equilibrium-and-dock2-recruitment-and-activation
#10
Jing Wang, Liling Xu, Samina Shaheen, Sichen Liu, Wenjie Zheng, Xiaolin Sun, Zhanguo Li, Wanli Liu
The growth of B cell receptor (BCR) microclusters upon antigen stimulation drives B cell activation. Here, we show that PI3K-mediated PIP3 production is required for the growth of BCR microclusters. This growth is likely inhibited by PTEN and dependent on its plasma membrane binding and lipid phosphatase activities. Mechanistically, we find that PIP3-dependent recruitment and activation of a guanine nucleotide exchange factor, Dock2, is required for the sustained growth of BCR microclusters through remodeling of the F-actin cytoskeleton...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29177249/smyd1c-mediates-cd8-t-cell-death-via-regulation-of-bcl2-mediated-restriction-of-outer-mitochondrial-membrane-integrity
#11
Hui Nie, Gary Rathbun, Haley Tucker
The SET and Mynd domain 1 (Smyd1) locus encodes three tissue-restricted isoforms. Two previously characterized isoforms, Smyd1A and Smyd1B, are heart and skeletal muscle-restricted histone methyl transferases. Here we report that a third, non-catalytic isoform, Smyd1C, is expressed predominantly in activated CD8 T cells. While Smyd1C- deficient CD8 T cells undergo activation-induced apoptosis, neither of two classical mechanisms activation-induced cell death nor activated cell autonomous death are utilized...
September 2017: Journal of Cell Signaling
https://www.readbyqxmd.com/read/29170669/introducing-membrane-charge-and-membrane-potential-to-t-cell-signaling
#12
REVIEW
Yuanqing Ma, Kate Poole, Jesse Goyette, Katharina Gaus
While membrane models now include the heterogeneous distribution of lipids, the impact of membrane charges on regulating the association of proteins with the plasma membrane is often overlooked. Charged lipids are asymmetrically distributed between the two leaflets of the plasma membrane, resulting in the inner leaflet being negatively charged and a surface potential that attracts and binds positively charged ions, proteins, and peptide motifs. These interactions not only create a transmembrane potential but they can also facilitate the formation of charged membrane domains...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29130972/human-dendritic-cells-with-th2-polarizing-capacity-analysis-using-label-free-quantitative-proteomics
#13
Leonie Hussaarts, Maria Mardalena Martini Kaisar, Arzu Tugce Guler, Hans Dalebout, Bart Everts, André M Deelder, Magnus Palmblad, Maria Yazdanbakhsh
BACKGROUND: Dendritic cells (DCs) are the sentinels of the immune system. Upon recognition of a pathogen, they mature and migrate to draining lymph nodes to prime and polarize T cell responses. Although it is known that helminths and helminth-derived molecules condition DCs to polarize T helper (Th) cells towards Th2, the underlying mechanisms remain incompletely understood. OBJECTIVES: The aim of this study was to conduct a proteome analysis of helminth antigen-stimulated DCs in order to gain more insight into the cellular processes associated with their ability to polarize immune responses...
2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29123958/expression-of-cd94-by-ex-vivo-differentiated-nk-cells-correlates-with-the-in-vitro-and-in-vivo-acquisition-of-cytotoxic-features
#14
Meriem Hasmim, Nadine Khalife, Yanyan Zhang, Manale Doldur, Geralidne Visentin, Stéphane Terry, Julien Giron-Michel, Ruoping Tang, François Delhommeau, Nicolas Dulphy, Jean-Henri Bourhis, Fawzia Louache, Salem Chouaib
The administration of ex vivo-expanded Natural Killer (NK) cells in leukemia therapy is still challenging, in part due to the difficulty to generate in sufficient quantities fully mature and functional NK cells and Identification of surface markers indicative of NK maturation and functionality is therefore needed. Here, based on the analysis of surface receptors of ex vivo-expanded NK cells, we identified CD94 as a surface marker correlating with high lytic potential against leukemic cell lines and immunological synapse formation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123650/transcellular-communication-at-the-immunological-synapse-a-vesicular-traffic-mediated-mutual-exchange
#15
REVIEW
Francesca Finetti, Chiara Cassioli, Cosima T Baldari
The cell's ability to communicate with the extracellular environment, with other cells, and with itself is a crucial feature of eukaryotic organisms. In the immune system, T lymphocytes assemble a specialized structure upon contact with antigen-presenting cells bearing a peptide-major histocompatibility complex ligand, known as the immunological synapse (IS). The IS has been extensively characterized as a signaling platform essential for T-cell activation. Moreover, emerging evidence identifies the IS as a device for vesicular traffic-mediated cell-to-cell communication as well as an active release site of soluble molecules...
2017: F1000Research
https://www.readbyqxmd.com/read/29120926/recent-insights-into-biological-functions-of-mammalian-bombesin-like-peptides-and-their-receptors
#16
Xiangping Qu, Hui Wang, Rujiao Liu
PURPOSE OF REVIEW: The current review highlights recent advances in physiological and pharmacological researches in biology of mammalian bombesin-like peptides (BLPs). RECENT FINDINGS: BLPs and their receptors were found to have regulatory roles in many biological processes in central nervous system. Two BLPs, neuromedin B and gastrin-releasing peptide (GRP), and their receptors are required for regulation of basal and induced sighing activity in rodents. This is the first study demonstrating central pathways involved in regulation of sighing activity...
February 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/29079742/dual-biomembrane-force-probe-enables-single-cell-mechanical-analysis-of-signal-crosstalk-between-multiple-molecular-species
#17
Lining Ju, Yunfeng Chen, Kaitao Li, Zhou Yuan, Baoyu Liu, Shaun P Jackson, Cheng Zhu
Conventional approaches for studying receptor-mediated cell signaling, such as the western blot and flow cytometry, are limited in three aspects: 1) The perturbing preparation procedures often alter the molecules from their native state on the cell; 2) Long processing time before the final readout makes it difficult to capture transient signaling events (<1 min); 3) The experimental environments are force-free, therefore unable to visualize mechanical signals in real time. In contrast to these methods in biochemistry and cell biology that are usually population-averaged and non-real-time, here we introduce a novel single-cell based nanotool termed dual biomembrane force probe (dBFP)...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29079655/reversible-transgene-expression-reduces-fratricide-and-permits-4-1bb-costimulation-of-car-t-cells-directed-to-t-cell-malignancies
#18
Maksim Mamonkin, Malini Mukherjee, Madhuwanti Srinivasan, Sandhya Sharma, Diogo Gomes-Silva, Feiyan Mo, Giedre Krenciute, Jordan S Orange, Malcolm K Brenner
T cells expressing second-generation chimeric antigen receptors (CARs) specific for CD5, a T-cell surface marker present on normal and malignant T cells, can selectively kill tumor cells. We aimed to improve this killing by substituting the CD28 costimulatory endodomain (28.z) with 4-1BB (BB.z), as 28.z CD5 CAR T cells rapidly differentiated into short-lived effector cells. In contrast, 4-1BB costimulation is known to promote development of the central memory subpopulation. Here, we found BB.z CD5 CAR T cells had impaired growth compared to 28...
October 27, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29042364/a-cd200r-cd28-fusion-protein-appropriates-an-inhibitory-signal-to-enhance-t-cell-function-and-therapy-of-murine-leukemia
#19
Shannon K Oda, Andrew W Daman, Nicolas M Garcia, Felecia Wagener, Thomas M Schmitt, Xiaoxia Tan, Aude G Chapuis, Philip D Greenberg
Acute myeloid leukemia (AML), the most common adult acute leukemia in the U.S., has the poorest survival rate, with 26% of patients surviving 5 years. Adoptive immunotherapy with T cells genetically modified to recognize tumors is a promising and evolving treatment option. However, antitumor activity, particularly in the context of progressive leukemia, can be dampened both by limited costimulation and triggering of immunoregulatory checkpoints that attenuate T cell responses. Expression of CD200 (OX2), a negative regulator of T cell function that binds CD200R, is commonly increased in leukemia and other malignancies, and is associated with poor prognosis in leukemia patients...
October 17, 2017: Blood
https://www.readbyqxmd.com/read/29027226/efferocytosis-of-dying-cells-differentially-modulate-immunological-outcomes-in-tumor-microenvironment
#20
REVIEW
Sushil Kumar, David Calianese, Raymond B Birge
Programmed cell death (apoptosis) is an integral part of tissue homeostasis in complex organisms, allowing for tissue turnover, repair, and renewal while simultaneously inhibiting the release of self antigens and danger signals from apoptotic cell-derived constituents that can result in immune activation, inflammation, and autoimmunity. Unlike cells in culture, the physiological fate of cells that die by apoptosis in vivo is their rapid recognition and engulfment by phagocytic cells (a process called efferocytosis)...
November 2017: Immunological Reviews
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