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TCR signalling

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https://www.readbyqxmd.com/read/28437578/klrg1-impairs-treg-competitive-fitness-in-the-gut
#1
Holger Meinicke, Anna Bremser, Maria Brack, Klaudia Schrenk, Hanspeter Pircher, Ana Izcue
Immune homeostasis requires the tight, tissue-specific control of the different CD4(+) Foxp3(+) regulatory T cells (Treg) populations. The cadherin-binding inhibitory receptor KLRG1 is expressed by a subpopulation of Treg with GATA3(+) effector phenotype. Although such Treg are important for the immune balance, especially in the gut, the role of KLRG1 in Treg has not been assessed. Using KLRG1 KO mice, we found that KLRG1 deficiency does not affect Treg frequencies in spleen, mesenteric lymph nodes or intestine, or frequencies of GATA3(+) Treg in the gut...
April 24, 2017: Immunology
https://www.readbyqxmd.com/read/28437437/use-of-short-interfering-rna-delivered-by-cationic-liposomes-to-enable-efficient-down-regulation-of-ptpn22-gene-in-human-t-lymphocytes
#2
Valentina Perri, Marsha Pellegrino, Francesca Ceccacci, Anita Scipioni, Stefania Petrini, Elena Gianchecchi, Anna Lo Russo, Serena De Santis, Giovanna Mancini, Alessandra Fierabracci
Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target...
2017: PloS One
https://www.readbyqxmd.com/read/28436433/pathways-and-genes-associated-with-immune-dysfunction-in-sheep-paratuberculosis
#3
Anton Gossner, Craig Watkins, Francesca Chianini, John Hopkins
Multibacillary and paucibacillary paratuberculosis are both caused by Mycobacterium avium subspecies paratuberculosis. Multibacillary lesions are composed largely of infected epithelioid macrophages and paucibacillary lesions contain T cells but few bacteria. Multibacillary disease is similar to human lepromatous leprosy, with variable/high levels of antibody and a dysfunctional immune response. Animals with paucibacillary disease have high cell-mediated immunity and variable levels of antibody. This study aims to characterize the immunological dysfunction using TruSeq analysis of the ileocaecal lymph node that drains disease lesions...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28433528/evolutionary-history-of-the-t-cell-receptor-complex-as-revealed-by-small-spotted-catshark-scyliorhinus-canicula
#4
Rita Pettinello, Anthony K Redmond, Christopher J Secombes, Daniel J Macqueen, Helen Dooley
In every jawed vertebrate species studied so far, the T cell receptor (TCR) complex is composed of two different TCR chains (α/β or γ/δ) and a number of CD3 subunits responsible for transmitting signals into the T cell. In this study, we characterised all of the TCR and CD3 genes of small-spotted catshark (Scyliorhinus canicula) and analysed their expression in a broad range of tissues. While the TCR complex is highly conserved across jawed vertebrates, we identified a number of differences in catshark, most notably the presence of two copies of both TCRβ and CD3γδ, and the absence of a functionally-important proline rich region from CD3ε...
April 19, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28428787/a-possible-role-for-idiotype-anti-idiotype-b-t-cell-interactions-in-maintaining-immune-memory
#5
Victor I Seledtsov, Galina V Seledtsova
Variable regions of both B-cell receptors (BCRs) and T-cell receptors (TCRs) are completely formed in the postnatal period, and, consequently, no innate immune tolerance against these structures exists in adulthood. Indeed, antibodies (Abs) specific to TCRs have been found in both animals and humans. These facts clearly indicate the existence of B cells able to directly interact with T cells through binding of BCRs to TCRs without implicating major histocompatibility complex molecules. A novel paradigm is proposed in that the immune memory is based on idiotype/anti-idiotype interactions occurring between BCRs and TCRs following clearance of the antigen that elicited immune responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28426533/hiv-dna-content-in-different-cd4-t-cell-subsets-correlates-with-cd4-cd8-ratio-or-length-of-efficient-treatment
#6
Lara Gibellini, Simone Pecorini, Sara de Biasi, Elena Bianchini, Margherita Digaetano, Marcello Pinti, Gianluca Carnevale, Vanni Borghi, Giovanni Guaraldi, Cristina Mussini, Andrea Cossarizza, Milena Nasi
OBJECTIVES: HIV establishes a latent infection at different degrees within naïve (TN) or central (TCM) and effector memory (TEM) CD4+ T cell. Studying patients in whom HIV production was suppressed by combined antiretroviral therapy (cART), our main aim was to find which factors are related or can influence intracellular viral reservoir in different CD4+ T cell subsets. METHODS: We enrolled 32 HIV+ patients successfully treated for > 2 years, with a CD4+ T cell count > 500 cells/μL and plasma viremia undetectable from at least one year...
April 19, 2017: AIDS
https://www.readbyqxmd.com/read/28415650/a-highly-conserved-redox-active-mx-2-cwx-6-r-motif-regulates-zap70-stability-and-activity
#7
Christoph Thurm, Mateusz P Poltorak, Elisa Reimer, Melanie M Brinkmann, Lars Leichert, Burkhart Schraven, Luca Simeoni
ζ-associated protein of 70 kDa (Zap70) is crucial for T-cell receptor (TCR) signaling. Loss of Zap70 in both humans and mice results in severe immunodeficiency. On the other hand, the expression of Zap70 in B-cell malignancies correlates with the severity of the disease. Because of its role in immune-related disorders, Zap70 has become a therapeutic target for the treatment of human diseases. It is well-established that the activity/expression of Zap70 is regulated by post-translational modifications of crucial amino acids including the phosphorylation of tyrosines and the ubiquitination of lysines...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28393253/recombinant-adenovirus-of-sea-and-cd80-genes-driven-by-mmre-and-mouse-tert-promoter-induce-effective-antitumor-immune-responses-against-different-types-of-tumor-cells-in%C3%A2-vitro-and-in%C3%A2-vivo
#8
Shao-Yan Si, Jun-Li Liu, Jun-Lian Liu, Bing-Xin Xu, Jian-Zhong Li, Ya-Ya Qin, Shu-Jun Song
Staphylococcus enterotoxin A (SEA) is a powerful immunostimulant and can stimulate T cells bearing certain T-cell receptor β-chain variable regions when bound to major histocompatibility complex II molecules. SEA is widely used in research of antitumor therapy. The low affinity T-cell receptor (TCR) interaction with SEA in the absence of MHC class II antigens is sufficient for the induction of cytotoxicity but requires additional CD28/B7 signaling to result in proliferation of resting T cells. In this study, we constructed recombinant adenovirus (named as Ad-MMRE-mTERT-BIS) carrying membrane-expressing SEA (named as SEAtm) and CD80 driven by Myc-Max response elements (MMRE) and mouse telomerase reverse transcriptase (mTERT) promoter to reduce toxicity and to improve safety and efficiency...
April 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28387753/imatinib-mesylate-inhibits-stat5-phosphorylation-in-response-to-il-7-and-promotes-t-cell-lymphopenia-in-chronic-myelogenous-leukemia-patients
#9
S Thiant, M M Moutuou, P Laflamme, R Sidi Boumedine, D M Leboeuf, L Busque, J Roy, M Guimond
Imatinib mesylate (IM) therapy has been shown to induce lower T cell counts in chronic myelogenous leukemia (CML) patients and an interference of IM with T cell receptor (TCR) signaling has been invoked to explain this observation. However, IL-7 and TCR signaling are both essential for lymphocyte survival. This study was undertaken to determine whether IM interferes with IL-7 or TCR signaling to explain lower T cell counts in patients. At diagnosis, CML patients have typically lower CD4(+) counts in their blood, yet CD8(+) counts are normal or even increased in some...
April 7, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28378044/yersinia-pseudotuberculosis-supports-th17-differentiation-and-limits-de-novo-regulatory-t-cell-induction-by-directly-interfering-with-t-cell-receptor-signaling
#10
Maria Pasztoi, Agnes Bonifacius, Joern Pezoldt, Devesha Kulkarni, Jana Niemz, Juhao Yang, René Teich, Janina Hajek, Fabio Pisano, Manfred Rohde, Petra Dersch, Jochen Huehn
Adaptive immunity critically contributes to control acute infection with enteropathogenic Yersinia pseudotuberculosis; however, the role of CD4(+) T cell subsets in establishing infection and allowing pathogen persistence remains elusive. Here, we assessed the modulatory capacity of Y. pseudotuberculosis on CD4(+) T cell differentiation. Using in vivo assays, we report that infection with Y. pseudotuberculosis resulted in enhanced priming of IL-17-producing T cells (Th17 cells), whereas induction of Foxp3(+) regulatory T cells (Tregs) was severely disrupted in gut-draining mesenteric lymph nodes (mLNs), in line with altered frequencies of tolerogenic and proinflammatory dendritic cell (DC) subsets within mLNs...
April 4, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28377772/treatment-of-pediatric-acute-graft-versus-host-disease-lessons-from-primary-immunodeficiency
#11
REVIEW
Aisling M Flinn, Andrew R Gennery
Allogeneic hematopoietic stem cell transplant (HSCT) is used to treat increasing numbers of malignant and non-malignant disorders. Despite significant advances in improved human leukocyte antigens-typing techniques, less toxic conditioning regimens and better supportive care, resulting in improved clinical outcomes, acute graft-versus-host disease (aGvHD) continues to be a major obstacle and, although it principally involves the skin, gastrointestinal tract, and liver, the thymus is also a primary target. An important aim following HSCT is to achieve complete and durable immunoreconstitution with a diverse T-cell receptor (TCR) repertoire to recognize a broad range of pathogens providing adequate long-term adaptive T-lymphocyte immunity, essential to reduce the risk of infection, disease relapse, and secondary malignancies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28356349/camp-a-multifaceted-modulator-of-immune-synapse-assembly-and-t-cell-activation
#12
REVIEW
Vijay Bharathi Arumugham, Cosima T Baldari
T Lymphocyte activation involves a substantial reorganization of the membranous and intracellular compartments. Signaling complexes assemble and dismantle in a highly ordered fashion in both compartments and orchestrate the activation of T cells with high sensitivity and specificity. TCR ligation leads to a short burst of cAMP production, which is centrally required for T cell activation; however, sustained elevations in intracellular cAMP concentrations are immunosuppressive. Emerging evidence of the existence of local cAMP pools gleaned from studies on other cell types suggests that cAMP compartmentalization may account, in part, for these opposing effects...
March 29, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28356069/broad-induction-of-immunoregulatory-mechanisms-after-a-short-course-of-anti-il-7r%C3%AE-antibodies-in-nod-mice
#13
Cristina Vazquez-Mateo, Justin Collins, Michelle Fleury, Hans Dooms
BACKGROUND: Type 1 diabetes is an autoimmune disease caused by T cell-mediated destruction of the insulin-producing β-cells in the pancreas. Therefore, approaches that effectively halt the pathogenic T cell response are predicted to have preventive or therapeutic benefit for type 1 diabetes patients. We previously demonstrated that long-term blocking of IL-7 signaling, which is critical for the survival and function of T cells, prevented and reversed type 1 diabetes in non-obese diabetic mice...
March 29, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28346410/quality-of-tcr-signaling-determined-by-differential-affinities-of-enhancers-for-the-composite-batf-irf4-transcription-factor-complex
#14
Arifumi Iwata, Vivek Durai, Roxane Tussiwand, Carlos G Briseño, Xiaodi Wu, Gary E Grajales-Reyes, Takeshi Egawa, Theresa L Murphy, Kenneth M Murphy
Variable strengths of signaling via the T cell antigen receptor (TCR) can produce divergent outcomes, but the mechanism of this remains obscure. The abundance of the transcription factor IRF4 increases with TCR signal strength, but how this would induce distinct types of responses is unclear. We compared the expression of genes in the TH2 subset of helper T cells to enhancer occupancy by the BATF-IRF4 transcription factor complex at varying strengths of TCR stimulation. Genes dependent on BATF-IRF4 clustered into groups with distinct TCR sensitivities...
May 2017: Nature Immunology
https://www.readbyqxmd.com/read/28344876/2b4-sap-signaling-is-required-for-the-priming-of-naive-cd8-t-cells-by-antigen-expressing-b-cells-and-b-lymphoma-cells
#15
Yu-Hsuan Huang, Kevin Tsai, Sara Y Tan, Sohyeong Kang, Mandy L Ford, Kenneth W Harder, John J Priatel
Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein-Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8(+) T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28340336/a-dna-based-t-cell-receptor-reveals-a-role-for-receptor-clustering-in-ligand-discrimination
#16
Marcus J Taylor, Kabir Husain, Zev J Gartner, Satyajit Mayor, Ronald D Vale
A T cell mounts an immune response by measuring the binding strength of its T cell receptor (TCR) for peptide-loaded MHCs (pMHC) on an antigen-presenting cell. How T cells convert the lifetime of the extracellular TCR-pMHC interaction into an intracellular signal remains unknown. Here, we developed a synthetic signaling system in which the extracellular domains of the TCR and pMHC were replaced with short hybridizing strands of DNA. Remarkably, T cells can discriminate between DNA ligands differing by a single base pair...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28337984/lipid-dependent-conformational-dynamics-underlie-the-functional-versatility-of-t-cell-receptor
#17
Xingdong Guo, Chengsong Yan, Hua Li, Wenmao Huang, Xiaoshan Shi, Min Huang, Yingfang Wang, Weiling Pan, Mingjun Cai, Lunyi Li, Wei Wu, Yibing Bai, Chi Zhang, Zhijun Liu, Xinyan Wang, Xiaohui F Zhang, Chun Tang, Hongda Wang, Wanli Liu, Bo Ouyang, Catherine C Wong, Yi Cao, Chenqi Xu
T-cell receptor-CD3 complex (TCR) is a versatile signaling machine that can initiate antigen-specific immune responses based on various biochemical changes of CD3 cytoplasmic domains, but the underlying structural basis remains elusive. Here we developed biophysical approaches to study the conformational dynamics of CD3ε cytoplasmic domain (CD3εCD). At the single-molecule level, we found that CD3εCD could have multiple conformational states with different openness of three functional motifs, i.e., ITAM, BRS and PRS...
April 2017: Cell Research
https://www.readbyqxmd.com/read/28337207/gastrointestinal-microbiome-dysbiosis-in-infant-mice-alters-peripheral-cd8-t-cell-receptor-signaling
#18
Gabriela Gonzalez-Perez, Esi S N Lamousé-Smith
We recently reported that maternal antibiotic treatment (MAT) of mice in the last days of pregnancy and during lactation dramatically alters the density and composition of the gastrointestinal microbiota of their infants. MAT infants also exhibited enhanced susceptibility to a systemic viral infection and altered adaptive immune cell activation phenotype and function. CD8(+) effector T cells from MAT infants consistently demonstrate an inability to sustain interferon gamma (IFN-γ) production in vivo following vaccinia virus infection and in vitro upon T cell receptor (TCR) stimulation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28333940/distinct-transcriptome-profiles-of-gag-specific-cd8-t-cells-temporally-correlated-with-the-protection-elicited-by-siv%C3%AE-nef-live-attenuated-vaccine
#19
Wuxun Lu, Yanmin Wan, Fangrui Ma, R Paul Johnson, Qingsheng Li
The live attenuated vaccine (LAV) SIVmac239Δnef (SIVΔnef) confers the best protection among all the vaccine modalities tested in rhesus macaque model of HIV-1 infection. This vaccine has a unique feature of time-dependent protection: macaques are not protected at 3-5 weeks post vaccination (WPV), whereas immune protection emerges between 15 and 20 WPV. Although the exact mechanisms of the time-dependent protection remain incompletely understood, studies suggested that both cellular and humoral immunities contribute to this time-dependent protection...
2017: PloS One
https://www.readbyqxmd.com/read/28333124/bap31-is-involved-in-t-cell-activation-through-tcr-signal-pathways
#20
Kunwei Niu, Jialin Xu, Yuhua Cao, Yue Hou, Mu Shan, Yanqing Wang, Yang Xu, Mingyi Sun, Bing Wang
BAP31 is a ubiquitously expressed endoplasmic reticulum (ER) membrane protein. The functions of BAP31 in the immune system have not been investigated due to the lack of animal models. Therefore we created a BAP31 conditional knockdown mouse by performing a knockdown of BAP31 in the thymus. In doing so, we demonstrate that the maturation of T cells is normal but the number of T cells is less in the thymus of the knockout mouse. In addition, the spleen and lymph nodes of peripheral immune organs contained a lesser proportion of the mature T cells in the thymus specific BAP31 knockout mice...
March 23, 2017: Scientific Reports
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