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Immunological Synapse (immunological + synapse)
Selected AbstractsPPP1R9B (Neurabin 2): Involvement and dynamics in the NK immunological synapseEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2009Xiaobo Meng Abstract The NK immunological synapse (NKIS) is a dynamic structure dependent on the assembly of membrane, cytoskeletal and signaling components. These serve to focus and generate stimuli for adhesion and orientation of the cytoskeleton for targeted cytolytic granule release. Previous studies have demonstrated the importance of the cytoskeleton in these processes. We previously identified PPP1R9B (neurabin 2, spinophilin) as a cytoskeletal component of the NK-like cell line YTS. We demonstrate that (i) PPP1R9B gradually accumulates at the NKIS in a maturation stage-dependent manner; (ii) it mimics the early kinetics of actin recruitment to the NKIS but it precedes actin departure from the site; (iii) it is recruited by CD18 stimulation but not by CD28 ligation; (iv) it is required for the maintenance of the cortical F-actin organization in the YTS cells and knocking down PPP1R9B reduces the frequency of YTS,target cell conjugation, possibly due to the collapsed F-actin cytoskeleton in these cells. These results indicate that PPP1R9B is required for synapse formation in the NK cells and suggest that it may be involved in the maintenance of cellular architecture by regulation of actin assembly, possibly acting to stabilize the NKIS until granule release is eminent. [source] Cover Picture , Eur.EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2006The cover has been specifically designed to introduce the 16th European Congress of Immunology. It combines a picture of the Eiffel Tower with a fluorescence microscopy image of immune cells, underlining the immunological research that will be discussed at the meeting. The immunofluorescence staining shows B lymphocytes (CD45 in red, IgM in blue) forming an immunological synapse with an antigen presenting cell (ICAM-1 in green) and was kindly provided by Yolanda Carrasco, Cancer Research UK, London. [source] Vav1 transduces TCR signals required for LFA-1 function and cell polarization at the immunological synapseEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2003Laurence Ardouin Abstract Activation of T lineage cells through the TCR by peptide,MHC complexes on APC is critically dependent on rearrangement of the actin cytoskeleton. Vav1 is a guanine nucleotide exchange factor for members of the Rho/Rac family of GTPases which is activated following TCR stimulation, suggesting that it may transduce TCR signals to the activation of some or all actin-controlled processes. Weshow that Vav1-deficient double-positive thymocytes are less efficient at forming conjugates with APC presenting agonist peptide than wild-type cells are. Furthermore we demonstrate that Vav1 is required for TCR-induced activation of the integrin LFA-1, which is likely to explain the defect in conjugate formation. However, once Vav1-deficient cells form a conjugate, the assembly of proteins into an immunological synapse at the conjugate interface is normal. In contrast, thymocyte polarization is defective in the absence of Vav1, as judged by the relocalization of the microtubule-organizing center. These data demonstrate that Vav1 transduces signals to only a subset of cytoskeleton-dependent events at the immunological synapse. [source] Dynamic regulation of T-cell costimulation through TCR,CD28 microclustersIMMUNOLOGICAL REVIEWS, Issue 1 2009Tadashi Yokosuka Summary:, T-cell activation requires contact between T cells and antigen-presenting cells (APCs) to bring T-cell receptors (TCRs) and major histocompatibility complex peptide (MHCp) together to the same complex. These complexes rearrange to form a concentric circular structure, the immunological synapse (IS). After the discovery of the IS, dynamic imaging technologies have revealed the details of the IS and provided important insights for T-cell activation. We have redefined a minimal unit of T-cell activation, the ,TCR microcluster', which recognizes MHCp, triggers an assembly of assorted molecules downstream of the TCR, and induces effective signaling from TCRs. The relationship between TCR signaling and costimulatory signaling was analyzed in terms of the TCR microcluster. CD28, the most valuable costimulatory receptor, forms TCR,CD28 microclusters in cooperation with TCRs, associates with protein kinase C ,, and effectively induces initial T-cell activation. After mature IS formation, CD28 microclusters accumulate at a particular subregion of the IS, where they continuously assemble with the kinases and not TCRs, and generate sustained T-cell signaling. We propose here a ,TCR,CD28 microcluster' model in which TCR and costimulatory microclusters are spatiotemporally formed at the IS and exhibit fine-tuning of T-cell responses by assembling with specific players downstream of the TCR and CD28. [source] Natural killer cell cytotoxicity: how do they pull the trigger?IMMUNOLOGY, Issue 1 2009Nicola J. Topham Summary Natural killer (NK) cells target and kill aberrant cells, such as virally infected and tumorigenic cells. Killing is mediated by cytotoxic molecules which are stored within secretory lysosomes, a specialized exocytic organelle found in NK cells. Target cell recognition induces the formation of a lytic immunological synapse between the NK cell and its target. The polarized exocytosis of secretory lysosomes is then activated and these organelles release their cytotoxic contents at the lytic synapse, specifically killing the target cell. The essential role that secretory lysosome exocytosis plays in the cytotoxic function of NK cells is highlighted by immune disorders that are caused by the mutation of critical components of the exocytic machinery. This review will discuss recent studies on the molecular basis for NK cell secretory lysosome exocytosis and the immunological consequences of defects in the exocytic machinery. [source] Normal and abnormal secretion by haemopoietic cellsIMMUNOLOGY, Issue 1 2001Jane C. Stinchcombe Summary The secretory lysosomes found in haemopoietic cells provide a very efficient mechanism for delivering the effector proteins of many immune cells in response to antigen recognition. Although secretion shows some similarities to the secretion of specialized granules in other secretory cell types, some aspects of secretory lysosome release appear to be unique to melanocytes and cells of the haemopoietic lineage. Mast cells and platelets have provided excellent models for studying secretion, but recent advances in characterizing the immunological synapse allow a very fine dissection of the secretory process in T lymphocytes. These studies show that secretory lysosomes are secreted from the centre of the talin ring at the synapse. Proper secretion requires a series of Rab and cytoskeletal elements which play critical roles in the specialized secretion of lysosomes in haemopoietic cells. [source] Involvement of HAb18G/CD147 in T cell activation and immunological synapse formationJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8 2010Jinsong Hu Abstract HAb18G/CD147, a glycoprotein of the immunoglobulin super-family (IgSF), is a T cell activation-associated molecule. In this report, we demonstrated that HAb18G/CD147 expression on both activated CD4+ and CD8+ T cells was up-regulated. In vitro cross-linking of T cells with an anti-HAb18G/CD147 monoclonal antibody (mAb) 5A12 inhibited T cells proliferation upon T cell receptor stimulation. Such co-stimulation inhibited T cell proliferation by down-regulating the expression of CD25 and interleukin-2 (IL-2), decreased production of IL-4 but not interferon-,. Laser confocal imaging analysis indicated that HAb18G/CD147 was recruited to the immunological synapse (IS) during T cell activation; triggering HAb18G/CD147 on activated T cells by anti-HAb18G/CD147 mAb 5A12 strongly dispersed the formation of the IS. Further functional studies showed that the ligation of HAb18G/CD147 with mAb 5A12 decreased the tyrosine phosphorylation and intracellular calcium mobilization levels of T cells. Through docking antibody,antigen interactions, we demonstrated that the function of mAb 5A12 is tightly dependent on its specificity of binding to N-terminal domain I, which plays pivotal role in the oligomerization of HAb18G/CD147. Taken together, we provide evidence that HAb18G/CD147 could act as a co-stimulatory receptor to negatively regulate T cell activation and is functionally linked to the formation of the IS. [source] | ||||||||||