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Relevant bibliographies by topics / T cells Receptors

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Academic literature on the topic 'T cells Receptors'

Author: Grafiati

Published: 4 June 2021

Last updated: 6 September 2023

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Journal articles on the topic "T cells Receptors"

1

Y, Elshimali. "Chimeric Antigen Receptor T-Cell Therapy (Car T-Cells) in Solid Tumors, Resistance and Success." Bioequivalence & Bioavailability International Journal 6, no. 1 (2022): 1–6. http://dx.doi.org/10.23880/beba-16000163.

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CARs are chimeric synthetic antigen receptors that can be introduced into an immune cell to retarget its cytotoxicity toward a specific tumor antigen. CAR T-cells immunotherapy demonstrated significant success in the management of hematologic malignancies. Nevertheless, limited studies are present regarding its efficacy in solid and refractory tumors. It is well known that the major concerns regarding this technique include the risk of relapse and the resistance of tumor cells, in addition to high expenses and limited affordability. Several factors play a crucial role in improving the efficacy of immunotherapy, including tumor mutation burden (TMB), microsatellite instability (MSI), loss of heterozygosity (LOH), the APOBEC Protein Family, tumor microenvironment (TMI), and epigenetics. In this minireview, we address the current and future applications of CAR T-Cells against solid tumors and their measure for factors of resistance and success.

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Meiliana, Anna, Nurrani Mustika Dewi, and Andi Wijaya. "CAR T Cells: Precision Cancer Immunotherapy." Indonesian Biomedical Journal 10, no. 3 (December 28, 2018): 203–16. http://dx.doi.org/10.18585/inabj.v10i3.635.

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BACKGROUND: Current cancer drugs and treatments are aiming at eradicating tumor cells, but often are more toxic then effective, killing also the normal cells and not selectively the tumor cells. There is good personalized cancer therapy that involves administration to the cancer-bearing host of immune cells with direct anticancer activity, which called adoptive cell therapy (ACT). A review of the unique biology of T cell therapy and of recent clinical experience compels a reassessment of target antigens that traditionally have been viewed from the perspective of weaker immunotherapeutic modalities.CONTENT: Chimeric antigen receptors (CAR) are recombinant receptors which provide both antigen-binding and T cell-activating functions. Many kind of CARs has been reported for the past few years, targeting an array of cell surface tumor antigens. Their biologic functions have extremely changed following the introduction of tripartite receptors comprising a costimulatory domain, termed second-generation CARs. The combination of CARs with costimulatory ligands, chimeric costimulatory receptors, or cytokines can be done to further enhance T cell potency, specificity and safety. CARs reflects a new class of drugs with exciting potential for cancer immunotherapy.SUMMARY: CAR-T cells have been arising as a new modality for cancer immunotherapy because of their potent efficacy against terminal cancers. They are known to exert higher efficacy than monoclonal antibodies and antibodydrug conjugates, and act via mechanisms distinct from T cell receptor-engineered T cells. These cells are constructed by transducing genes encoding fusion proteins of cancer antigen-recognizing single-chain Fv linked to intracellular signaling domains of T cell receptors.KEYWORDS: chimeric antigen receptor, CAR T cells, adoptive cell therapy, ACT, T cell receptor, TCR, cancer, immunotherapy

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Steverding, Dietmar. "Cycle Numbers of Cell Surface Recycling Receptors." Receptors 2, no. 2 (June 6, 2023): 160–65. http://dx.doi.org/10.3390/receptors2020010.

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The cycle number (nc) of a recycling receptor is defined as the average number of round trips (cell surface–endosome–cell surface) the receptor can make before it is degraded. This characteristic parameter of recycling receptors can be easily determined from the receptor’s half-life (t½, the time in which 50% of the receptor is degraded) and cycling time (Tc, the time a receptor needs to complete a round trip). Relationship analyses revealed that nc increases linearly with increasing t½ and decreases exponentially with increasing Tc. For commonly observed t½ and Tc values, it was calculated that recycling receptors have nc values of <300. In addition, it was found that recycling receptors in cancer cells have generally smaller nc values (<100), whereas recycling receptors in normal cells have larger nc values (>100). Based on this latter finding, the cycle number nc may be a useful criterion for distinguishing between cancer and normal cells.

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Coico, R. F., B. Xue, D. Wallace, B. Pernis, G. W. Siskind, and G. J. Thorbecke. "T cells with receptors for IgD." Nature 316, no. 6030 (August 1985): 744–46. http://dx.doi.org/10.1038/316744a0.

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Klein, Thomas W., Cathy Newton, Kellie Larsen, Joe Chou, Izabella Perkins, Lily Lu, Liang Nong, and Herman Friedman. "Cannabinoid receptors and T helper cells." Journal of Neuroimmunology 147, no. 1-2 (February 2004): 91–94. http://dx.doi.org/10.1016/j.jneuroim.2003.10.019.

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Rossig, Claudia, Catherine M. Bollard, Jed G. Nuchtern, Cliona M. Rooney, and Malcolm K. Brenner. "Epstein-Barr virus–specific human T lymphocytes expressing antitumor chimeric T-cell receptors: potential for improved immunotherapy." Blood 99, no. 6 (March 15, 2002): 2009–16. http://dx.doi.org/10.1182/blood.v99.6.2009.

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Abstract Primary T cells expressing chimeric receptors specific for tumor or viral antigens have considerable therapeutic potential. Unfortunately, their clinical value is limited by their rapid loss of function and failure to expand in vivo, presumably due to the lack of costimulator molecules on tumor cells and the inherent limitations of signaling exclusively through the chimeric receptor. Epstein-Barr virus (EBV) infection of B lymphocytes is near universal in humans and stimulates high levels of EBV-specific helper and cytotoxic T cells, which persist indefinitely. Our clinical studies have shown that EBV-specific T cells generated in vitro will expand, persist, and function for more than 6 years in vivo. We now report that EBV-specific (but not primary) T cells transduced with tumor-specific chimeric receptor genes can be expanded and maintained long-term in the presence of EBV-infected B cells. They recognize EBV-infected targets through their conventional T-cell receptor and tumor targets through their chimeric receptors. They efficiently lyse both. EBV-specific T cells expressing chimeric antitumor receptors may represent a new source of effector cells that would persist and function long-term after their transfer to cancer patients.

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Sato, Noriko, Richard N. Bamford, Bonita R. Bryant, Yutaka Tagaya, and Thomas A. Waldmann. "Accessory cells precondition naive T cells and regulatory T cells for cytokine-mediated proliferation." Journal of Immunology 210, no. 1_Supplement (May 1, 2023): 164.02. http://dx.doi.org/10.4049/jimmunol.210.supp.164.02.

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Abstract Naïve T cells and regulatory T cells, when purified, do not proliferate to the common cytokine receptor γ-chain family cytokines interleukin (IL)-2, IL-7 or IL-15, despite their expression of cognate cytokine receptors. Cell-to-cell contact with dendritic cells (DCs) enabled proliferation of the T cell to these cytokines, independent of antigen recognition or T cell receptor stimulation. This effect lasted after separation of T cells from DCs, enabling enhanced proliferation of the T cells in mice depleted of DCs. We propose calling this a “preconditioning effect”. Interestingly, IL-2 alone was sufficient to induce phosphorylation and nuclear translocation of STAT5 in T cells, but could not activate MAPK and AKT pathways and failed to induce transcription of IL-2-target genes. Preconditioning was necessary to activate these two pathways, and induced weak Ca 2+mobilization independent of calcium release-activated channels. When preconditioning was combined with IL-2, full activation of downstream mTOR, 4E-BP1 hyperphosphorylation and prolonged S6 phosphorylation occurred, and T cells underwent proliferation. Collectively, accessory cells provide T cell preconditioning, a unique activation mechanism, controlling cytokine-mediated proliferation of T cells.

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Suzuki, T., and M. D. Cooper. "Comparison of the expression of IL 2 receptors by human T and B cells: induction by the polyclonal mitogens, phorbol myristate acetate, and anti-mu antibody." Journal of Immunology 134, no. 5 (May 1, 1985): 3111–19. http://dx.doi.org/10.4049/jimmunol.134.5.3111.

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Abstract It is well established that IL 2 plays an important role in the proliferative response of T cells. Activated B cells were also recently found to express IL 2 receptors. The present studies were designed to compare qualitative, quantitative, and functional aspects of IL 2 receptor expression by activated T and B cells. Phorbol myristate acetate (PMA)-activated human T and small resting B cells and enhanced the expression of HLA-DR, HLA-DC/DS, and transferrin receptors while reducing Leu-4 antigen expression by T cells and IgM and IgD expression on B cells. PMA induced both T and B cells to express functional IL 2 receptors before cellular proliferation. Immune interferon did not participate in this induction. The m.w. of the IL 2 receptors expressed by activated T and B cells was identical: 54,000 to 59,000. Several differences were noted in the expression of IL 2 receptors by activated T and B cells on stimulation with PMA; T cells expressed IL 2 receptors sooner than B cells and in higher density, and the enhanced proliferative response of T cells to IL 2 was more difficult to inhibit with antibody to IL 2 receptors. In addition, IL 2 enhanced the expression of transferrin receptors by activated T cells but did not have a similar effect on activated B cells. Small B cells from the blood could also be induced by a mitogenic monoclonal anti-IgM antibody to express functional IL 2 receptors. Relatively large B cells in fresh blood samples were found to express functional IL 2 receptors and were capable of a modest proliferative response to IL 2. The intensity of the IL 2 receptor expression and the proliferative response by large B cells were enhanced by PMA stimulation. The data suggest that IL 2 receptors may play an auxiliary role in the B cell proliferative response and that IL 2 may exert its effect at a late phase in the B cell activation process.

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Scheurich, P., B. Thoma, U. Ucer, and K. Pfizenmaier. "Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNF-alpha-mediated enhancement of T cell responses." Journal of Immunology 138, no. 6 (March 15, 1987): 1786–90. http://dx.doi.org/10.4049/jimmunol.138.6.1786.

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Abstract The expression of specific tumor necrosis factor (TNF) membrane receptors and biological effects of recombinant TNF (rTNF)-alpha on normal human T lymphocytes were studied. Although resting T cells lacked specific binding capacity for rTNF-alpha, high affinity (Kd 70 pM) TNF receptors were de novo induced upon primary activation of T cells. Comparison of TNF receptor expression with that of high affinity interleukin 2 (IL-2) and interferon-gamma (IFN-gamma) receptors, respectively, revealed similarities to IL 2-receptor expression with respect to kinetics of induction. However, maximum expression of TNF receptors (approximately equal to 5000/cell at day 6) and subsequent decline occurred approximately 3 days after the peak of IL 2-receptor expression. In contrast, no change in the expression of IFN-gamma receptors (Kd 10 pM, 300 to 400 receptors/cell) was found in the course of T cell activation. On activated TNF receptor positive T cells, TNF-alpha exerted multiple stimulatory activities. Thus TNF increased the expression of HLA-DR antigens and high affinity IL 2 receptors. As a consequence, TNF-treated T cells showed an enhanced proliferative response to IL 2. Moreover, TNF-alpha was effective as a co-stimulator of IL 2-dependent IFN-gamma production. These data indicate that TNF-alpha may regulate growth and functional activities of normal T cells.

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Aune, T. M., K. M. McGrath, T. Sarr, M. P. Bombara, and K. A. Kelley. "Expression of 5HT1a receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-hydroxytryptamine." Journal of Immunology 151, no. 3 (August 1, 1993): 1175–83. http://dx.doi.org/10.4049/jimmunol.151.3.1175.

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Abstract The neurotransmitter, serotonin (5-hydroxytryptamine, 5HT), has been shown to affect function of cells of the immune system. More recently, specific 5HT receptors have been identified and partially characterized on Jurkat cells. Results presented here characterize the receptor on Jurkat cells as the 5HT1a receptor subtype and show that mitogen-activated but not resting human T cells also express the 5HT1a receptor subtype. Analysis of mRNA in Jurkat cells and activated and resting T cells by PCR or by Northern analysis revealed the presence of 5HT1a receptor. Pharmacologic analysis of this receptor demonstrated that the receptors on Jurkat cells and activated T cells are similar to each other and that they resemble the 5HT1a receptor found in the brain. Analysis of the second messenger pathways activated by the 5HT1a receptor show that ligand-binding to the Jurkat cell 5HT1a receptor results in elevation of intracellular inositol phosphates and Ca2+ and that ligand binding to the 5HT1a receptor on activated T cells modulated intracellular levels of cAMP.

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Dissertations / Theses on the topic "T cells Receptors"

1

Soper, David Michael. "Interleukin-2 receptor and T cell receptor signaling in regulatory T cells /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/8344.

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Carson, Bryan David. "Impaired T cell receptor signaling in regulatory T cells /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/8337.

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Ebert, Lisa Michelle. "The regulation of chemokine receptor expression upon T lymphocyte activation." Title page, contents and abstract only, 2002. http://web4.library.adelaide.edu.au/theses/09PH/09phe165.pdf.

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Parra, Eduardo. "Molecular basis for costimulation of human T lymphocytes." Lund : Lund University, 1998. http://books.google.com/books?id=SgFrAAAAMAAJ.

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Carlsson, Fredrik. "Antibody Feedback Regulation and T Cells." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7631.

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Tanaka, Yujiro. "Selection of T cells in the thymus." Thesis, University College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294749.

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Chan, Ping-lung, and 陳秉隆. "Roles of TLR5 and ICOS on the human allogenic CD40-activated B cell-induced CD4hiCD25+ regulatory T cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47149735.

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Neeraj. "Studies on equine helper T cells and Fcγ receptors." Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627077.

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Crocker, Glenn. "A study of surface receptors on rat T lymphocytes." Thesis, University of Oxford, 1991. http://ora.ox.ac.uk/objects/uuid:5c74a70b-1f5e-4c78-904f-7c4ff1b543a8.

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A double immunolabelling technique was developed to study microscopically the interactions between CD4, CD45 and the T cell receptor on the surface of rat T cells induced by the phenomenon of co-capping. It was found that both CD4 and CD45 passively co-cap with the actively capped T cell receptor, that the T cell receptor and CD45 passively co-cap with CD4, but that neither CD4 nor the T cell receptor co-cap with CD45. Co-crosslinking and active capping of CD45 with either the T cell receptor or CD4 prevented CD4 or the T cell receptor respectively, from passively co-capping. These experiments were extended to study the effects of particular antibody crosslinking conditions on T cell proliferation and tyrosine phosphorylation. A correlation was found to exist between receptor distribution and the effects of particular antibody combinations on proliferation and tyrosine phosphorylation. The significance of this with respect to T cell activation is discussed. Finally, an observation is reported concerning the failure of some cell lines to cap antibody-crosslinked surface molecules. Preliminary investgations into the nature and extent of the phenomenon are described.

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Jiang, Ning. "Kinetic analysis of Fcγ receptor and T cell receptor interacting with respective ligands." Diss., Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/26716.

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Low affinity Fcg receptor III (FcgRIII, CD16) triggers a variety of cellular events upon binding to the Fc portion of IgG. A real-time flow cytometry method was developed to measure the affinity and kinetics of such low affinity receptor/ligand interactions, which was shown as an easily operated yet powerful tool. Results revealed an unusual temperature dependence of reverse rate of CD16aTM dissociating from IgG. Except for a few studies using mammalian cell CD16s, most kinetics analyses use purified aglycosylated extracellular portion of the molecules, making it impossible to assess the importance of the receptor anchor and glycosylation on ligand binding. We used a micropipette adhesion frequency assay to demonstrate that the anchor length affects the forward rate and affinity of CD16s for IgG in a species specific manner, most likely through conformational changes. Receptor glycosylation dramatically reduced ligand binding by 100 folds. T cell receptor (TCR) is arguably the most important receptor in the adaptive human immune system. Together with coreceptor CD4 or CD8, TCR can discriminate different antigen peptides complexed with major histocompatibility complex (MHC) molecule (pMHC), which differ by as few as only one amino acid, and trigger different T cell responses. When T cell signaling was suppressed, TCR had similar affinity and kinetics for agonist and antagonist pMHC whose binding to CD8 was undetectable. TCR on activated T cell had a higher affinity for pMHCs, suggesting that TCRs organize themselves differently on activated T cells than on naïve T cells. In the absence of inhibitors for signaling, TCR binds agonist pMHC with several orders of magnitude higher affinity than antagonist pMHC. In addition, engagement of TCR by pMHC signals an upregulation of CD8 binding to pMHC, which is much stronger than the TCR-pMHC binding. The transition from weak TCR binding to the strong CD8 binding takes place around 0.75 second after TCR in contact with pMHC and can be reduced by several inhibitors of tyrosine and lipid phosphorylation, membrane rafts, and actin cytoskeleton. These results provide new insights to understanding T cell discrimination.

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Books on the topic "T cells Receptors"

1

1945-, Mak Tak W., ed. The T-cell receptors. New York: Plenum Press, 1988.

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Brondz, Boris Davydovich. T lymphocytes and their receptors in immunologic recognition. London, Eng: Harwood Academic Publishers, 1988.

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3

M, Davis Mark, Kappler John, University of California, Los Angeles., and UCLA Symposium on the T Cell Receptor (1987 : Keystone, Colo.), eds. The T-cell receptor: Proceedings of a Smith Kline & French-UCLA symposium, held in Keystone, Colorado, April 26-May 1, 1987. New York: A.R. Liss, 1988.

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R, Oksenberg Jorge, ed. The antigen T cell receptor: Selected protocols and applications. New York: R.G. Landes, 1997.

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1932-, Haber Edgar, ed. Antigen binding molecules: Antibodies and T-cell receptors. San Diego: Academic Press, 1996.

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Dimitrov, Dimiter S. HIV and membrane receptors. New York: Chapman & Hall, 1997.

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M, Davis Mark, and Buxbaum Joel, eds. T-cell receptor use in human autoimmune diseases. New York, N.Y: New York Academy of Sciences, 1995.

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Van den Elsen, Peter J., 1951-. The human T-cell receptor repertoire and transplantation. New York: Springer Verlag, 1995.

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Marc, Feldmann, Lamb Jonathan R, and Woody James N, eds. Human T cell clones: A new approach to immune regulation. Clifton, N.J: Humana Press, 1985.

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Jean-François, Bach, ed. T-cell-directed immunointervention. Oxford [England]: Blackwell Scientific Publications, 1993.

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Book chapters on the topic "T cells Receptors"

1

Sandor, M., and R. G. Lynch. "FcγR on T cells." In The Immunoglobulin Receptors and their Physiological and Pathological Roles in Immunity, 169–83. Dordrecht: Springer Netherlands, 1998. http://dx.doi.org/10.1007/978-94-011-5018-7_16.

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Moretta, A., S. Sivori, M. Ponte, M. C. Mingari, and L. Moretta. "Stimulatory Receptors in NK and T Cells." In Specificity, Function, and Development of NK Cells, 15–23. Berlin, Heidelberg: Springer Berlin Heidelberg, 1998. http://dx.doi.org/10.1007/978-3-642-46859-9_2.

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Mage, Rose G., and Claire Rogel-Gaillard. "Immunogenetics in the rabbit." In The genetics and genomics of the rabbit, 66–83. Wallingford: CABI, 2021. http://dx.doi.org/10.1079/9781780643342.0005.

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Abstract This chapter on immunogenetics in the rabbit focused on some genes with genetic and genomic sequence information including those encoding: soluble circulating immunoglobulin molecules (Igs) and their surface-bound forms on B lymphocytes (BCRs); T-cell receptors on T lymphocyte surfaces, (TCRs); the rabbit Leukocyte Antigen (RLA) complex (proteins on cells that function to present antigen fragments to TCRs); and some cytokine genes that encode key regulators of T- and B-cell responses.

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Anfossi, Nicolas, Véronique Pascal, Sophie Ugolini, and Eric Vivier. "Characterization of Tm1 cells, a NKR+ subset of memory-phenotype CD8+ T cells." In Activating and Inhibitory Immunoglobulin-like Receptors, 225–34. Tokyo: Springer Japan, 2001. http://dx.doi.org/10.1007/978-4-431-53940-7_28.

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Williams, J. M., and T. B. Strom. "De Novo Expression of Receptors on T Cells." In Handbook of Experimental Pharmacology, 37–52. Berlin, Heidelberg: Springer Berlin Heidelberg, 1988. http://dx.doi.org/10.1007/978-3-642-73217-1_3.

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Rapoport, Aaron P., and Jean A. Yared. "T Cell Receptors-Gene-Modified T Cells for Cancer: Methods, Data, and Challenges." In Advances and Controversies in Hematopoietic Transplantation and Cell Therapy, 109–33. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-54368-0_7.

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Modlin, Robert L., Julie Lewis, Koichi Uyemura, and Robert E. Tigelaar. "T Lymphocytes Bearing Gamma-Delta Antigen Receptors in Skin." In Heat-Shock Proteins and Gamma-Delta T Cells, 61–74. Basel: KARGER, 1992. http://dx.doi.org/10.1159/000319103.

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Hellmeier, Joschka, René Platzer, Johannes B. Huppa, and Eva Sevcsik. "A DNA Origami-Based Biointerface to Interrogate the Spatial Requirements for Sensitized T-Cell Antigen Recognition." In The Immune Synapse, 277–302. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-3135-5_18.

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AbstractWhen T cells scan the surface of antigen-presenting cells (APCs), they can detect the presence of just a few antigenic peptide/MHC complexes (pMHCs), in some cases even a single agonist pMHC. These are typically vastly outnumbered by structurally similar yet non-stimulatory endogenous pMHCs. How T cells achieve this enormous sensitivity and selectivity is still not clear, in particular in view of the rather moderate (1–100 μM) affinity that T-cell receptors (TCRs) typically exert for antigenic pMHCs. Experimental approaches that enable the control and quantification of physical input parameters within the context of the immunological synapse to precisely interrogate the molecular consequences of TCR-engagement, appear highly advantageous when searching for better answers.We here describe the implementation of a biointerface that allows to experimentally define molecular distances between T-cell ligands as a means to correlate them with molecular dynamics of antigen engagement, downstream signaling, and the overall T-cell response. The basis of this biointerface is DNA origami nanostructures, which are (i) rigid and highly versatile platforms that can (ii) be embedded as laterally mobile entities within supported lipid bilayers and functionalized (iii) in a site-specific and orthogonal manner with (iv) one or more proteins of choice.

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Ferrick, David A., and Lorraine Gemmell-Hori. "Potential Developmental Role for Self-Reactive T Cells Bearing Gamma-Delta T Cell Receptors Specific for Heat-Shock Proteins." In Heat-Shock Proteins and Gamma-Delta T Cells, 17–31. Basel: KARGER, 1992. http://dx.doi.org/10.1159/000319100.

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Marinez-A., C., J. M. Alonso, Alicia Barcena, P. Aparicio, and Maria L. Toribio. "From the Developmental Expression of γδ T Cell Receptors to the Implications in the Acquisition of Tolerance." In Function and Specificity of γ/δ T Cells, 17–23. Berlin, Heidelberg: Springer Berlin Heidelberg, 1991. http://dx.doi.org/10.1007/978-3-642-76492-9_3.

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Conference papers on the topic "T cells Receptors"

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Chang, ZeNan L., Pamela A. Silver, and Yvonne Y. Chen. "Abstract B022: Functional bifurcation in T cells expressing chimeric antigen receptors." In Abstracts: CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/2326-6074.cricimteatiaacr15-b022.

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Strijker, JGM, E. Drent, JJF van der Hoek, R. Pscheid, B. Koopmans, K. Ober, SR van Hooff, et al. "P06.01 αβ-T cells engineered to express γδ-T cell receptors can kill neuroblastoma organoids independent of MHC-I expression." In iTOC8 – the 8th Leading International Cancer Immunotherapy Conference in Europe, 8–9 October 2021, Virtual Conference. BMJ Publishing Group Ltd, 2021. http://dx.doi.org/10.1136/jitc-2021-itoc8.35.

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Gavin, Marc A., Alexander Gragerov, Erik Espling, Alex Rohde, Tim Sexton, Christiana Doulami, and George Gaitanaris. "Abstract B45: Phosphatidylserine suppresses T cells through GPR174, and co-inhibition of adenosine receptors and GPR174 synergistically enhances T cell responses." In Abstracts: AACR Special Conference on Tumor Immunology and Immunotherapy; November 17-20, 2019; Boston, MA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/2326-6074.tumimm19-b45.

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Lu, Binfeng, Min Yang, Wenwen Du, Wensi Zhai, Runzi Sun, Cuihua Yue, and Jingting Jiang. "Abstract B06: Immune inhibitory receptors restrain hyperactivated effector T cells in the tumor microenvironment." In Abstracts: AACR Special Conference on Tumor Immunology and Immunotherapy; November 27-30, 2018; Miami Beach, FL. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/2326-6074.tumimm18-b06.

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Smith, Duane, Payal Watchmaker, Guido Stadler, Natalie Marks, Yelena Bronevetsky, Keviin Chapman, and Hideho Okada. "Abstract 5773: Sequencing and cloning IDH1 R132H-targeted monoclonal T cell receptors from CD4+T cells facilitated by opto-electric-positioning technology." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-5773.

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Nadigel, J., D. Prefontaine, J. Bourbeau, F. Maltais, D. Eidelman, and Q. Hamid. "The Expression of Toll-Like Receptors in CD8+T Cells in Chronic Obstructive Pulmonary Disease." In American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California. American Thoracic Society, 2009. http://dx.doi.org/10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a1005.

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Yu, Yingyan, Eva Brudy, Rabea Imker, Cornelia Dalibor, Oliver Eickelberg, and Susanne Krauss-Etschmann. "Upregulation Of Pulmonary Chemokine Receptor 2 (CCR2) Positive T Cells And Their Chemokine Receptors Profile In Bleomycin-Induced Lung Fibrosis." In American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a5397.

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Chang, Lung-Ji, Yuchen Liu, and Jan S. Moreb. "Abstract 2796: Engineering multiple chimeric antigen receptors in T cells for the treatment of multiple myeloma." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-2796.

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Bergamini, Alice, Elena Tassi, Miriam Sant’Angelo, Chiara Balestrieri, Emanuela Brunetto, Miriam Redegalli, Alessia Potenza, et al. "2022-RA-1651-ESGO Epithelial Ovarian Cancer is infiltrated by activated effector T cells coexpressing multiple inhibitory receptors and by myeloid cells expressing inhibitory receptor ligands." In ESGO 2022 Congress. BMJ Publishing Group Ltd, 2022. http://dx.doi.org/10.1136/ijgc-2022-esgo.901.

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Nishiyama, Shuhei, Amy Wright, Itay Lotan, Friedemann Paul, and Michael Levy. "Upregulated complement receptors correlate with Fc gamma receptor 3A-positive natural killer cells (NK) and natural killer-T cells (NKT) in neuromyelitis optica spectrum disorder. (S50.003)." In 2023 Annual Meeting Abstracts. Lippincott Williams & Wilkins, 2023. http://dx.doi.org/10.1212/wnl.0000000000203565.

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Reports on the topic "T cells Receptors"

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Tzfira, Tzvi, Michael Elbaum, and Sharon Wolf. DNA transfer by Agrobacterium: a cooperative interaction of ssDNA, virulence proteins, and plant host factors. United States Department of Agriculture, December 2005. http://dx.doi.org/10.32747/2005.7695881.bard.

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Agrobacteriumtumefaciensmediates genetic transformation of plants. The possibility of exchanging the natural genes for other DNA has led to Agrobacterium’s emergence as the primary vector for genetic modification of plants. The similarity among eukaryotic mechanisms of nuclear import also suggests use of its active elements as media for non-viral genetic therapy in animals. These considerations motivate the present study of the process that carries DNA of bacterial origin into the host nucleus. The infective pathway of Agrobacterium involves excision of a single-stranded DNA molecule (T-strand) from the bacterial tumor-inducing plasmid. This transferred DNA (T-DNA) travels to the host cell cytoplasm along with two virulence proteins, VirD2 and VirE2, through a specific bacteriumplant channel(s). Little is known about the precise structure and composition of the resulting complex within the host cell and even less is known about the mechanism of its nuclear import and integration into the host cell genome. In the present proposal we combined the expertise of the US and Israeli labs and revealed many of the biophysical and biological properties of the genetic transformation process, thus enhancing our understanding of the processes leading to nuclear import and integration of the Agrobacterium T-DNA. Specifically, we sought to: I. Elucidate the interaction of the T-strand with its chaperones. II. Analyzing the three-dimensional structure of the T-complex and its chaperones in vitro. III. Analyze kinetics of T-complex formation and T-complex nuclear import. During the past three years we accomplished our goals and made the following major discoveries: (1) Resolved the VirE2-ssDNA three-dimensional structure. (2) Characterized VirE2-ssDNA assembly and aggregation, along with regulation by VirE1. (3) Studied VirE2-ssDNA nuclear import by electron tomography. (4) Showed that T-DNA integrates via double-stranded (ds) intermediates. (5) Identified that Arabidopsis Ku80 interacts with dsT-DNA intermediates and is essential for T-DNA integration. (6) Found a role of targeted proteolysis in T-DNA uncoating. Our research provide significant physical, molecular, and structural insights into the Tcomplex structure and composition, the effect of host receptors on its nuclear import, the mechanism of T-DNA nuclear import, proteolysis and integration in host cells. Understanding the mechanical and molecular basis for T-DNA nuclear import and integration is an essential key for the development of new strategies for genetic transformation of recalcitrant plant species. Thus, the knowledge gained in this study can potentially be applied to enhance the transformation process by interfering with key steps of the transformation process (i.e. nuclear import, proteolysis and integration). Finally, in addition to the study of Agrobacterium-host interaction, our research also revealed some fundamental insights into basic cellular mechanisms of nuclear import, targeted proteolysis, protein-DNA interactions and DNA repair.

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Altstein, Miriam, and Ronald J. Nachman. Rational Design of Insect Control Agent Prototypes Based on Pyrokinin/PBAN Neuropeptide Antagonists. United States Department of Agriculture, August 2013. http://dx.doi.org/10.32747/2013.7593398.bard.

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The general objective of this study was to develop rationally designed mimetic antagonists (and agonists) of the PK/PBAN Np class with enhanced bio-stability and bioavailability as prototypes for effective and environmentally friendly pest insect management agents. The PK/PBAN family is a multifunctional group of Nps that mediates key functions in insects (sex pheromone biosynthesis, cuticular melanization, myotropic activity, diapause and pupal development) and is, therefore, of high scientific and applied interest. The objectives of the current study were: (i) to identify an antagonist biophores (ii) to develop an arsenal of amphiphilic topically active PK/PBAN antagonists with an array of different time-release profiles based on the previously developed prototype analog; (iii) to develop rationally designed non-peptide SMLs based on the antagonist biophore determined in (i) and evaluate them in cloned receptor microplate binding assays and by pheromonotropic, melanotropic and pupariation in vivo assays. (iv) to clone PK/PBAN receptors (PK/PBAN-Rs) for further understanding of receptor-ligand interactions; (v) to develop microplate binding assays for screening the above SMLs. In the course of the granting period A series of amphiphilic PK/PBAN analogs based on a linear lead antagonist from the previous BARD grant was synthesized that incorporated a diverse array of hydrophobic groups (HR-Suc-A[dF]PRLa). Others were synthesized via the attachment of polyethylene glycol (PEG) polymers. A hydrophobic, biostablePK/PBAN/DH analog DH-2Abf-K prevented the onset of the protective state of diapause in H. zea pupae [EC50=7 pmol/larva] following injection into the preceding larval stage. It effectively induces the crop pest to commit a form of ‘ecological suicide’. Evaluation of a set of amphiphilic PK analogs with a diverse array of hydrophobic groups of the formula HR-Suc-FTPRLa led to the identification of analog T-63 (HR=Decyl) that increased the extent of diapause termination by a factor of 70% when applied topically to newly emerged pupae. Another biostablePK analog PK-Oic-1 featured anti-feedant and aphicidal properties that matched the potency of some commercial aphicides. Native PK showed no significant activity. The aphicidal effects were blocked by a new PEGylated PK antagonist analog PK-dF-PEG4, suggesting that the activity is mediated by a PK/PBAN receptor and therefore indicative of a novel and selective mode-of-action. Using a novel transPro mimetic motif (dihydroimidazole; ‘Jones’) developed in previous BARD-sponsored work, the first antagonist for the diapause hormone (DH), DH-Jo, was developed and shown to block over 50% of H. zea pupal diapause termination activity of native DH. This novel antagonist development strategy may be applicable to other invertebrate and vertebrate hormones that feature a transPro in the active core. The research identifies a critical component of the antagonist biophore for this PK/PBAN receptor subtype, i.e. a trans-oriented Pro. Additional work led to the molecular cloning and functional characterization of the DH receptor from H. zea, allowing for the discovery of three other DH antagonist analogs: Drosophila ETH, a β-AA analog, and a dF analog. The receptor experiments identified an agonist (DH-2Abf-dA) with a maximal response greater than native DH. ‘Deconvolution’ of a rationally-designed nonpeptide heterocyclic combinatorial library with a cyclic bis-guanidino (BG) scaffold led to discovery of several members that elicited activity in a pupariation acceleration assay, and one that also showed activity in an H. zea diapause termination assay, eliciting a maximal response of 90%. Molecular cloning and functional characterization of a CAP2b antidiuretic receptor from the kissing bug (R. prolixus) as well as the first CAP2b and PK receptors from a tick was also achieved. Notably, the PK/PBAN-like receptor from the cattle fever tick is unique among known PK/PBAN and CAP2b receptors in that it can interact with both ligand types, providing further evidence for an evolutionary relationship between these two NP families. In the course of the granting period we also managed to clone the PK/PBAN-R of H. peltigera, to express it and the S. littoralis-R Sf-9 cells and to evaluate their interaction with a variety of PK/PBAN ligands. In addition, three functional microplate assays in a HTS format have been developed: a cell-membrane competitive ligand binding assay; a Ca flux assay and a whole cell cAMP ELISA. The Ca flux assay has been used for receptor characterization due to its extremely high sensitivity. Computer homology studies were carried out to predict both receptor’s SAR and based on this analysis 8 mutants have been generated. The bioavailability of small linear antagonistic peptides has been evaluated and was found to be highly effective as sex pheromone biosynthesis inhibitors. The activity of 11 new amphiphilic analogs has also been evaluated. Unfortunately, due to a problem with the Heliothis moth colony we were unable to select those with pheromonotropic antagonistic activity and further check their bioavailability. Six peptides exhibited some melanotropic antagonistic activity but due to the low inhibitory effect the peptides were not further tested for bioavailability in S. littoralis larvae. Despite the fact that no new antagonistic peptides were discovered in the course of this granting period the results contribute to a better understanding of the interaction of the PK/PBAN family of Nps with their receptors, provided several HT assays for screening of libraries of various origin for presence of PK/PBAN-Ragonists and antagonists and provided important practical information for the further design of new, peptide-based insecticide prototypes aimed at the disruption of key neuroendocrine physiological functions in pest insects.

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Baszler, Timothy, Igor Savitsky, Christopher Davies, Lauren Staska, and Varda Shkap. Identification of bovine Neospora caninum cytotoxic T-lymphocyte epitopes for development of peptide-based vaccine. United States Department of Agriculture, March 2006. http://dx.doi.org/10.32747/2006.7695592.bard.

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The goal of the one-year feasibility study was to identify specific cytotoxic T-lymphocyte (CTL) epitopes to Neosporacaninum in the natural bovine host in order to make progress toward developing an effective peptide-based vaccine against bovine neosporosis. We tested the hypothesis that: N. caninum SRS2 peptides contain immunogenicCTLepitope clusters cross-presented by multiple bovine MHC-I and MHC-IIhaplotypes. The specific objectives were: (1) Map bovine CTLepitopes of N. caninum NcSRS-2 and identify consensus MHC-I and class-II binding motifs; and (2) Determine if subunit immunization with peptides containing N. caninum-specificCTLepitopes cross-reactive to multiple bovine MHChaplotypes induces a CTL response in cattle with disparate MHChaplotypes. Neosporosis is a major cause of infectious abortion and congenital disease in cattle, persisting in cattle herds via vertical transmission.5 N. caninum abortions are reported in Israel; a serological survey of 52 Israeli dairy herds with reported abortions indicated a 31% infection rate in cows and 16% infection rate in aborted fetuses.9,14 Broad economic loss due to bovine neosporosis is estimated at $35,000,000 per year in California, USA, and $100,000,000 (Australian) per year in Australia and New Zealand.13 Per herd losses in a Canadian herd of 50 cattle are estimated more conservatively at $2,305 (Canadian) annually.4 Up to date practical measures to reduce losses from neosporosis in cattle have not been achieved. There is no chemotherapy available and, although progress has been made toward understanding immunity to Neospora infections, no efficacious vaccine is available to limit outbreaks or prevent abortions. Vaccine development to prevent N. caninum abortion and congenital infection remains a high research priority. To this end, our research group has over the past decade: 1) Identified the importance of T-lymphocyte-mediated immunity, particularly IFN-γ responses, as necessary for immune protection to congenital neosporosis in mice,1,2,10,11 and 2) Identified MHC class II restricted CD4+ CTL in Neosporainfected Holstein cattle,16 and 3) Identified NcSRS2 as a highly conserved surface protein associated with immunity to Neospora infections in mice and cattle.7,8,15 In this BARD-funded 12 month feasibility study, we continued our study of Neospora immunity in cattle and successfully completed T-lymphocyte epitope mapping of NcSRS2 surface protein with peptides and bovine immune cells,15 fulfilling objective 1. We also documented the importance of immune responses NcSRS2 by showing that immunization with native NcSRS2 reduces congenital Neospora transmission in mice,7 and that antibodies to NcSRS2 specifically inhibition invasion of placental trophoblasts.8 Most importantly we showed that T-lymphocyte responses similar to parasite infection, namely induction of activated IFN-γ secreting Tlymphocytes, could be induced by subunit immunization with NcSRS2 peptides containing the Neospora-specificCTLepitopes (Baszler et al, In preparation) fulfilling objective 2. Both DNA and peptide-based subunit approaches were tested. Only lipopeptide-based NcSRS2 subunits, modified with N-terminal linked palmitic acid to enhance Toll-like receptors 2 and 1 (TLR2-TLR1), stimulated robust antigen-specific T-lymphocyte proliferation, IFN-γ secretion, and serum antibody production across different MHC-IIhaplotypes. The discovery of MHC-II cross-reactive T-cellinducing parasite peptides capable of inducing a potentially protective immune response following subunit immunization in cattle is of significant practical importance to vaccine development to bovine neosporosis. In addition, our findings are more widely applicable in future investigations of protective T-cell, subunit-based immunity against other infectious diseases in outbred cattle populations.

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Weinberg, Andrew D. Tumor Specific CD4+ T-Cell Costimulation Through a Novel Receptor/Ligand Interaction. Fort Belvoir, VA: Defense Technical Information Center, August 1999. http://dx.doi.org/10.21236/ada374764.

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Wiley, Don C., and David N. Garboczi. Structural Analysis of the Human T-Cell Receptor/HLA-A2/Peptide Complex. Fort Belvoir, VA: Defense Technical Information Center, August 1997. http://dx.doi.org/10.21236/ada342257.

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Weinberg, Andrew D. Tumor Specific CD4+ T-Cell Costimulation Through a Novel Receptor Ligand Interaction. Fort Belvoir, VA: Defense Technical Information Center, August 1998. http://dx.doi.org/10.21236/ada359629.

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Gray, Andrew. Enhancing the Efficacy of Prostate Cancer Immunotherapy by Manipulating T-Cell Receptor Signaling in Order to Alter Peripheral Regulatory T-Cell Activity. Fort Belvoir, VA: Defense Technical Information Center, July 2009. http://dx.doi.org/10.21236/ada511997.

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Gray, Andrew. Enhancing the Efficacy of Prostate Cancer Immunotherapy by Manipulating T-Cell Receptor Signaling in Order to Alter Peripheral Regulatory T-Cell Activity. Fort Belvoir, VA: Defense Technical Information Center, July 2011. http://dx.doi.org/10.21236/ada553485.

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Fluhr, Robert, and Maor Bar-Peled. Novel Lectin Controls Wound-responses in Arabidopsis. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7697123.bard.

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Innate immune responses in animals and plants involve receptors that recognize microbe-associated molecules. In plants, one set of this defense system is characterized by large families of TIR–nucleotide binding site–leucine-rich repeat (TIR-NBS-LRR) resistance genes. The direct interaction between plant proteins harboring the TIR domain with proteins that transmit and facilitate a signaling pathway has yet to be shown. The Arabidopsis genome encodes TIR-domain containing genes that lack NBS and LRR whose functions are unknown. Here we investigated the functional role of such protein, TLW1 (TIR LECTIN WOUNDRESPONSIVE1). The TLW1 gene encodes a protein with two domains: a TIR domain linked to a lectin-containing domain. Our specific aim in this proposal was to examine the ramifications of the TL1-glycan interaction by; A) The functional characterization of TL1 activity in the context of plant wound response and B) Examine the hypothesis that wounding induced specific polysaccharides and examine them as candidates for TL-1 interactive glycan compounds. The Weizmann group showed TLW1 transcripts are rapidly induced by wounding in a JA-independent pathway and T-DNA-tagged tlw1 mutants that lack TLW1 transcripts, fail to initiate the full systemic wound response. Transcriptome methodology analysis was set up and transcriptome analyses indicates a two-fold reduced level of JA-responsive but not JA-independent transcripts. The TIR domain of TLW1 was found to interact directly with the KAT2/PED1 gene product responsible for the final b-oxidation steps in peroxisomal-basedJA biosynthesis. To identify potential binding target(s) of TL1 in plant wound response, the CCRC group first expressed recombinant TL1 in bacterial cells and optimized conditions for the protein expression. TL1 was most highly expressed in ArcticExpress cell line. Different types of extraction buffers and extraction methods were used to prepare plant extracts for TL1 binding assay. Optimized condition for glycan labeling was determined, and 2-aminobenzamide was used to label plant extracts. Sensitivity of MALDI and LC-MS using standard glycans. THAP (2,4,6- Trihydroxyacetophenone) showed minimal background peaks at positive mode of MALDI, however, it was insensitive with a minimum detection level of 100 ng. Using LC-MS, sensitivity was highly increased enough to detect 30 pmol concentration. However, patterns of total glycans displayed no significant difference between different extraction conditions when samples were separated with Dionex ICS-2000 ion chromatography system. Transgenic plants over-expressing lectin domains were generated to obtain active lectin domain in plant cells. Insertion of the overexpression construct into the plant genome was confirmed by antibiotic selection and genomic DNA PCR. However, RT-PCR analysis was not able to detect increased level of the transcripts. Binding ability of azelaic acid to recombinant TL1. Azelaic acid was detected in GST-TL1 elution fraction, however, DHB matrix has the same mass in background signals, which needs to be further tested on other matrices. The major findings showed the importance of TLW1 in regulating wound response. The findings demonstrate completely novel and unexpected TIR domain interactions and reveal a control nexus and mechanism that contributes to the propagation of wound responses in Arabidopsis. The implications are to our understanding of the function of TIR domains and to the notion that early molecular events occur systemically within minutes of a plant sustaining a wound. A WEB site (http://genome.weizmann.ac.il/hormonometer/) was set up that enables scientists to interact with a collated plant hormone database.

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Zhao, Kangjia, Jiwen Sun, Nanping Shen, Mengxue He, Haishan Ruan, Geng Lin, Jiali Ma, and Yanhua Xu. Treatment-Related Adverse Events of Chimeric Antigen receptor T-Cell (CAR-T) Cell Therapy in B-cell hematological malignancies in the Pediatric and Young Adult Population: A Systematic Review and Meta-Analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, July 2022. http://dx.doi.org/10.37766/inplasy2022.7.0034.

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