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https://www.readbyqxmd.com/read/28805806/lung-tumor-exome-files-with-t-cell-receptor-recombinations-a-mouse-model-of-t-cell-infiltrates-reflecting-mutation-burdens
#1
Yaping N Tu, Wei Lue Tong, Timothy J Fawcett, George Blanck
Tumor exomes and RNASeq data were originally intended for obtaining tumor mutations and gene expression profiles, respectively. However, recent work has determined that tumor exome and RNAseq read files contain reads representing T-cell and B-cell receptor (TcR and BcR) recombinations, presumably due to infiltrating lymphocytes. Furthermore, the recovery of immune receptor recombination reads has demonstrated correlations with specific, previously appreciated aspects of tumor immunology. To further understand the usefulness of recovering TcR and BcR recombinations from tumor exome files, we developed a scripted algorithm for recovery of reads representing these recombinations from a previously described mouse model of lung tumorigenesis...
August 14, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28804489/normalized-synergy-predicts-that-cd8-co-receptor-contribution-to-t-cell-receptor-tcr-and-pmhc-binding-decreases-as-tcr-affinity-increases-in-human-viral-specific-t-cells
#2
Chad M Williams, Alexandra A Schonnesen, Shu-Qi Zhang, Ke-Yue Ma, Chenfeng He, Tori Yamamoto, S Gail Eckhardt, Christopher A Klebanoff, Ning Jiang
The discovery of naturally occurring T cell receptors (TCRs) that confer specific, high-affinity recognition of pathogen and cancer-associated antigens remains a major goal in cellular immunotherapies. The contribution of the CD8 co-receptor to the interaction between the TCR and peptide-bound major histocompatibility complex (pMHC) has previously been correlated with the activation and responsiveness of CD8(+) T cells. However, these studies have been limited to model systems of genetically engineered hybridoma TCRs or transgenic mouse TCRs against either a single epitope or an array of altered peptide ligands...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28803850/association-of-exposure-to-manganese-and-iron-with-striatal-and-thalamic-gaba-and-other-neurometabolites-neuroimaging-results-from-the-weldox-ii-study
#3
Swaantje Casjens, Urike Dydak, Shalmali Dharmadhikari, Anne Lotz, Martin Lehnert, Clara Quetscher, Christoph Stewig, Benjamin Glaubitz, Tobias Schmidt-Wilcke, David Edmondson, Chien-Lin Yeh, Tobias Weiss, Christoph van Thriel, Lennard Herrmann, Siegfried Muhlack, Dirk Woitalla, Michael Aschner, Thomas Brüning, Beate Pesch
OBJECTIVE: Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men. MATERIAL AND METHODS: GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites...
August 10, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28798979/mucosa-associated-invariant-t-cells-infiltrate-hepatic-metastases-in-patients-with-colorectal-carcinoma-but-are-rendered-dysfunctional-within-and-adjacent-to-tumor-microenvironment
#4
Christopher R Shaler, Mauro E Tun-Abraham, Anton I Skaro, Khashayarsha Khazaie, Alexandra J Corbett, Tina Mele, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Mucosa-associated invariant T (MAIT) cells are innate-like T lymphocytes that are unusually abundant in the human liver, a common site of colorectal carcinoma (CRC) metastasis. However, whether they contribute to immune surveillance against colorectal liver metastasis (CRLM) is essentially unexplored. In addition, whether MAIT cell functions can be impacted by chemotherapy is unclear. These are important questions given MAIT cells' potent immunomodulatory and inflammatory properties. Herein, we examined the frequencies and functions of peripheral blood, healthy liver tissue, tumor-margin and tumor-infiltrating MAIT cells in 21 CRLM patients who received no chemotherapy, FOLFOX, or a combination of FOLFOX and Avastin before they underwent liver resection...
August 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28798028/ptpn2-regulates-t-cell-lineage-commitment-and-%C3%AE-%C3%AE-versus-%C3%AE-%C3%AE-specification
#5
Florian Wiede, Jarrod A Dudakov, Kun-Hui Lu, Garron T Dodd, Tariq Butt, Dale I Godfrey, Andreas Strasser, Richard L Boyd, Tony Tiganis
In the thymus, hematopoietic progenitors commit to the T cell lineage and undergo sequential differentiation to generate diverse T cell subsets, including major histocompatibility complex (MHC)-restricted αβ T cell receptor (TCR) T cells and non-MHC-restricted γδ TCR T cells. The factors controlling precursor commitment and their subsequent maturation and specification into αβ TCR versus γδ TCR T cells remain unclear. Here, we show that the tyrosine phosphatase PTPN2 attenuates STAT5 (signal transducer and activator of transcription 5) signaling to regulate T cell lineage commitment and SRC family kinase LCK and STAT5 signaling to regulate αβ TCR versus γδ TCR T cell development...
August 10, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28794279/nasopharyngeal-infection-by-streptococcus-pyogenes-requires-superantigen-responsive-v%C3%AE-specific-t-cells
#6
Joseph J Zeppa, Katherine J Kasper, Ivor Mohorovic, Delfina M Mazzuca, S M Mansour Haeryfar, John K McCormick
The globally prominent pathogen Streptococcus pyogenes secretes potent immunomodulatory proteins known as superantigens (SAgs), which engage lateral surfaces of major histocompatibility class II molecules and T-cell receptor (TCR) β-chain variable domains (Vβs). These interactions result in the activation of numerous Vβ-specific T cells, which is the defining activity of a SAg. Although streptococcal SAgs are known virulence factors in scarlet fever and toxic shock syndrome, mechanisms by how SAgs contribute to the life cycle of S...
August 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28783691/characterization-of-t-and-b-cell-repertoire-diversity-in-patients-with-rag-deficiency
#7
Yu Nee Lee, Francesco Frugoni, Kerry Dobbs, Irit Tirosh, Likun Du, Francesca A Ververs, Heng Ru, Lisa Ott de Bruin, Mehdi Adeli, Jacob H Bleesing, David Buchbinder, Manish J Butte, Caterina Cancrini, Karin Chen, Sharon Choo, Reem A Elfeky, Andrea Finocchi, Ramsay L Fuleihan, Andrew R Gennery, Dalia H El-Ghoneimy, Lauren A Henderson, Waleed Al-Herz, Elham Hossny, Robert P Nelson, Sung-Yun Pai, Niraj C Patel, Shereen M Reda, Pere Soler-Palacin, Raz Somech, Paolo Palma, Hao Wu, Silvia Giliani, Jolan E Walter, Luigi D Notarangelo
Recombination-activating genes 1 and 2 (RAG1 and RAG2) play a critical role in T and B cell development by initiating the recombination process that controls the expression of T cell receptor (TCR) and immunoglobulin genes. Mutations in the RAG1 and RAG2 genes in humans cause a broad spectrum of phenotypes, including severe combined immunodeficiency (SCID) with lack of T and B cells, Omenn syndrome, leaky SCID, and combined immunodeficiency with granulomas or autoimmunity (CID-G/AI). Using next-generation sequencing, we analyzed the TCR and B cell receptor (BCR) repertoire in 12 patients with RAG mutations presenting with Omenn syndrome (n = 5), leaky SCID (n = 3), or CID-G/AI (n = 4)...
December 16, 2016: Science Immunology
https://www.readbyqxmd.com/read/28781259/-the-influence-of-methylprednisolone-on-the-ability-of-cd4-sup-sup-cd95-sup-sup-hla-dr-sup-sup-t-cells-to-produce-proinflammatory-medators-in-cultures-of-tcr-activated-cd3-sup-sup-cd45ro-sup-sup-t-lymphocytes-from-patients-with-rheumatoid-arthritis
#8
N M Todosenko, O G Khaziakhmatova, K A Yurova, I P Malinina, L S Litvinova
The effect of different concentrations of the glucocorticoid (GC) methylprednisolone (MP) on CD4+CD95+HLA-DR+ T-cells and their ability to produce proinflammatory mediators in cultures of TCR-stimulated CD3+CD45RO+ T-lymphocytes in the in vitro system was investigated. T cells were obtained from healthy donors and patients with rheumatoid arthritis (RA).Under conditions of TCR-activation, MP increased the number of CD4+HLA-DR+CD95+ cells in CD3+CD45RO+ cultures obtained from RA patients and did not change their content in the control group...
May 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28775213/lactobacillus-reuteri-induces-gut-intraepithelial-cd4-cd8%C3%AE-%C3%AE-t-cells
#9
Luisa Cervantes-Barragan, Jiani N Chai, Ma Diarey Tianero, Blanda DiLuccia, Philip P Ahern, Joseph Merriman, Victor S Cortez, Michael G Caparon, Mohamed S Donia, Susan Gilfillan, Marina Cella, Jeffrey I Gordon, Chyi-Song Hsieh, Marco Colonna
The small intestine contains CD4(+)CD8αα(+) double-positive intraepithelial T lymphocytes (DP IELs), which originate from intestinal CD4(+) T cells through downregulation of the transcription factor ThPOK and have regulatory functions. DP IELs are absent in germ-free mice, suggesting that their differentiation depends on microbial factors. We found that DP IEL numbers in mice varied in different vivaria, correlating with the presence of Lactobacillus reuteri This species induced DP IELs in germ-free mice and conventionally raised mice lacking these cells...
August 3, 2017: Science
https://www.readbyqxmd.com/read/28771705/selected-signalling-proteins-recruited-to-the-t-cell-receptor-cd3-complex
#10
REVIEW
Jatuporn Ngoenkam, Wolfgang Schamel, Sutatip Pongcharoen
The T cell receptor (TCR)-CD3 complex, expressed on T cells, determines the outcome of a T cell response. It consists of the TCRαβ heterodimer and the non-covalently associated signalling dimers of CD3εγ, CD3εδ and CD3ζζ. TCRαβ binds specifically to a cognate peptide antigen bound to a major histocompatibility complex (MHC) molecule, whereas the CD3 subunits transmit the signal into the cytosol to activate signalling events. Recruitment of proteins to specialized localizations is one mechanism to regulate activation and termination of signalling...
August 3, 2017: Immunology
https://www.readbyqxmd.com/read/28767728/crystal-structure-of-qa-1a-with-bound-qa-1-determinant-modifier-peptide
#11
Ge Ying, Jing Wang, Vipin Kumar, Dirk M Zajonc
Qa-1 is a non-classical Major Histocompatibility (MHC) class I molecule that generally presents hydrophobic peptides including Qdm derived from the leader sequence of classical MHC I molecules for immune surveillance by NK cells. Qa-1 bound peptides derived from the TCR Vβ8.2 of activated T cells also activates CD8+ regulatory T cells to control autoimmunity and maintain self-tolerance. Four allotypes of Qa-1 (Qa-1a-d) are expressed that are highly conserved in sequence but have several variations that could affect peptide binding to Qa-1 or TCR recognition...
2017: PloS One
https://www.readbyqxmd.com/read/28765585/multi-color-single-molecule-tracking-and-subtrajectory-analysis-for-quantification-of-spatiotemporal-dynamics-and-kinetics-upon-t-cell-activation
#12
Yuma Ito, Kumiko Sakata-Sogawa, Makio Tokunaga
The dynamic properties of molecules in living cells are attracting increasing interest. We propose a new method, moving subtrajectory analysis using single-molecule tracking, and demonstrate its utility in the spatiotemporal quantification of not only dynamics but also the kinetics of interactions using single-color images. Combining this technique with three-color simultaneous single-molecule imaging, we quantified the dynamics and kinetics of molecules in spatial relation to T cell receptor (TCR) microclusters, which trigger TCR signaling...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28761757/mechanisms-of-action-and-rationale-for-the-use-of-checkpoint-inhibitors-in-cancer
#13
REVIEW
Clemence Granier, Eleonore De Guillebon, Charlotte Blanc, Helene Roussel, Cecile Badoual, Elia Colin, Antonin Saldmann, Alain Gey, Stephane Oudard, Eric Tartour
The large family of costimulatory molecules plays a crucial role in regulation of the immune response. These molecules modulate TCR signalling via phosphorylation cascades. Some of the coinhibitory members of this family, such as PD-1 and CTLA-4, already constitute approved targets in cancer therapy and, since 2011, have opened a new area of antitumour immunotherapy. Many antibodies targeting other inhibitory receptors (Tim-3, VISTA, Lag-3 and so on) or activating costimulatory molecules (OX40, GITR and so on) are under evaluation...
2017: ESMO Open
https://www.readbyqxmd.com/read/28761447/molecular-mechanisms-of-immunomodulation-properties-of-mesenchymal-stromal-cells-a-new-insight-into-the-role-of-icam-1
#14
Yury Rubtsov, Кirill Goryunov, Аndrey Romanov, Yulia Suzdaltseva, George Sharonov, Vsevolod Tkachuk
Mesenchymal stromal cells (MSC) control excessive inflammation and create a microenvironment for tissue repair protecting from chronic inflammation and tissue fibrosis. We examined the molecular mechanisms of MSC immunomodulatory function in mixed cultures of human adipose-derived MSC with lymphocytes. Our data show that MSC promote unstimulated lymphocyte survival potentially by an increase in antigen presentation. Under inflammatory conditions, mimicked by stimulation of TCR in lymphocytes, MSC suppress activation and proliferation of stimulated T cells...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28754817/multifaceted-role-of-btla-in-the-control-of-cd8-t-cell-fate-after-antigen-encounter
#15
Krit Ritthipichai, Cara Haymaker, Melisa Martinez-Paniagua, Andrew Aschenbrenner, Xiaohui Yi, Minying Zhang, Charuta Kale, Yared Hailemichael, Willem W Overwijk, Luis Vence, Jason Roszik, Navin Varadarajan, Roza Nurieva, Laszlo G Radvanyi, Patrick Hwu, Chantale Bernatchez
Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown an overall clinical response rate 40-50% in metastatic melanoma patients. BTLA (B-and-T lymphocyte attenuator) expression on transferred CD8(+) TIL was associated with better clinical outcome. The suppressive function of the ITIM and ITSM motifs of BTLA is well described. Here, we sought to determine the functional characteristics of the CD8(+)BTLA(+)TIL subset and define the contribution of the Grb2 motif of BTLA in T cell co-stimulation...
July 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28750779/pro-inflammatory-dual-receptor-t-cells-in-chronic-graft-versus-host-disease
#16
Amritha Balakrishnan, Nicholas Gloude, Roman Sasik, Edward D Ball, Gerald P Morris
Defective post-transplant thymopoiesis is associated with chronic graft versus host disease (cGVHD), a multi-organ pathology affecting up to 80% of patients following allogeneic hematopoietic stem cell transplantation (HSCT). Previous work demonstrated that the subset of T cells expressing two T cell receptors (TCRs) is predisposed to alloreactivity, driving selective and disproportionate activity in acute GVHD in both mouse models and HSCT patients. Here we investigate a potential role for this pathogenic T cell subset in cGVHD...
July 24, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28747670/pkc-%C3%B1-is-dispensable-for-ox40l-induced-tcr-independent-treg-proliferation-but-contributes-by-enabling-il-2-production-from-effector-t-cells
#17
Khaled Alharshawi, Alejandra Marinelarena, Prabhakaran Kumar, Osama El-Sayed, Palash Bhattacharya, Zuoming Sun, Alan L Epstein, Ajay V Maker, Bellur S Prabhakar
We have previously shown that OX40L/OX40 interaction is critical for TCR-independent selective proliferation of Foxp3(+) Tregs, but not Foxp3(-) effector T-cells (Teff), when CD4(+) T-cells are co-cultured with GM-CSF derived bone marrow dendritic cells (G-BMDCs). Events downstream of OX40L/OX40 interaction in Tregs responsible for this novel mechanism are not understood. Earlier, OX40L/OX40 interaction has been shown to stimulate CD4(+) T-cells through the formation of a signalosome involving TRAF2/PKC-Ѳ leading to NF-kB activation...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28746867/tcr-signal-quality-modulates-fate-decisions-of-single-cd4-t-cells-in-a-probabilistic-manner
#18
Yi-Li Cho, Michael Flossdorf, Lorenz Kretschmer, Thomas Höfer, Dirk H Busch, Veit R Buchholz
To what extent the lineage decisions of activated CD4(+) T cells are determined by the quality of T cell receptor (TCR) ligation is incompletely understood. Here, we show that individual T cells expressing identical TCRs take highly variable fate decisions despite binding the same ligand. We identify a mathematical model that correctly captures this probabilistic behavior and allows one to formalize changes in TCR signal quality-due to cognate versus altered peptide ligation-as changes of lineage-specific proliferation and differentiation rates...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28745331/cd47-blockade-enhances-therapeutic-activity-of-tcr-mimic-antibodies-to-ultra-low-density-cancer-epitopes
#19
M D Mathias, J T Sockolosky, A Y Chang, K S Tan, C Liu, K C Garcia, D A Scheinberg
Leukemia accepted article preview online, 12 July 2017. doi:10.1038/leu.2017.223.
July 12, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28743432/high-levels-of-eukaryotic-initiation-factor-6-eif6-are-required-for-immune-system-homeostasis-and-for-steering-the-glycolytic-flux-of-tcr-stimulated-cd4-t-cells-in-both-mice-and-humans
#20
Nicola Manfrini, Sara Ricciardi, Annarita Miluzio, Maya Fedeli, Alessandra Scagliola, Simone Gallo, Daniela Brina, Thure Adler, Dirk H Busch, Valerie Gailus-Durner, Helmut Fuchs, Martin Hrabě de Angelis, Stefano Biffo
Eukaryotic Initiation Factor 6 (eIF6) is required for 60S ribosomal subunit biogenesis and efficient initiation of translation. Intriguingly, in both mice and humans, endogenous levels of eIF6 are detrimental as they act as tumor and obesity facilitators, raising the question on the evolutionary pressure that maintains high eIF6 levels. Here we show that, in mice and humans, high levels of eIF6 are required for proper immune functions. First, eIF6 heterozygous (het) mice show an increased mortality during viral infection and a reduction of peripheral blood CD4(+) Effector Memory T cells...
July 22, 2017: Developmental and Comparative Immunology
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