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https://www.readbyqxmd.com/read/29106410/generation-of-higher-affinity-t-cell-receptors-by-antigen-driven-differentiation-of-progenitor-t-cells-in-vitro
#1
Thomas M Schmitt, David H Aggen, Kumiko Ishida-Tsubota, Sebastian Ochsenreither, David M Kranz, Philip D Greenberg
Many promising targets for T-cell-based cancer immunotherapies are self-antigens. During thymic selection, T cells bearing T cell receptors (TCRs) with high affinity for self-antigen are eliminated. The affinity of the remaining low-avidity TCRs can be improved to increase their antitumor efficacy, but conventional saturation mutagenesis approaches are labor intensive, and the resulting TCRs may be cross-reactive. Here we describe the in vitro maturation and selection of mouse and human T cells on antigen-expressing feeder cells to develop higher-affinity TCRs...
November 6, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/29097495/ebv-associated-primary-nodal-t-nk-cell-lymphoma-shows-distinct-molecular-signature-and-copy-number-changes
#2
Siok-Bian Ng, Tae-Hoon Chung, Seiichi Kato, Shigeo Nakamura, Emiko Takahashi, Young-Hyeh Ko, Joseph D Khoury, C Cameron Yin, Richie Soong, Anand D Jeyasekharan, Michal Marek Hoppe, Viknesvaran Selvarajan, Soo-Yong Tan, Soon-Thye Lim, Choon-Kiat Ong, Maarja-Liisa Nairismägi, Priyanka Maheshwari, Shoa-Nian Choo, Shuangyi Fan, Chi-Kuen Lee, Shih-Sung Chuang, Wee-Joo Chng
The molecular biology of primary nodal T- and NK-cell lymphoma and its relationsihp with extranodal NK/T-cell lymphoma, nasal type is poorly understood. In this study, we assessed the relationship between nodal and extranodal EBV-positive T/NK-cell lymphomas using gene expression profiling and copy number aberration analyses. We performed GEP and CNA analysis on 66 cases of EBV-associated T/NK-cell lymphoma from nodal and extranodal sites, and correlated the molecular signatures with clinicopathologic features...
November 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28830578/characterization-of-demodex-musculi-infestation-associated-comorbidities-and-topographic-distribution-in-a-mouse-strain-with-defective-adaptive-immunity
#3
Melissa A Nashat, Kerith R Luchins, Michelle L Lepherd, Elyn R Riedel, Joanna N Izdebska, Neil S Lipman
A colony of B6.Cg-Rag1tm1Mom Tyrp1B-w Tg(Tcra,Tcrb)9Rest (TRP1/TCR) mice presented with ocular lesions and ulcerative dermatitis. Histopathology, skin scrapes, and fur plucks confirmed the presence of Demodex spp. in all clinically affected and subclinical TRP1/TCR mice examined (n = 48). Pasteurella pneumotropica and Corynebacterium bovis, both opportunistic pathogens, were cultured from the ocular lesions and skin, respectively, and bacteria were observed microscopically in abscesses at various anatomic locations (including retroorbital sites, tympanic bullae, lymph nodes, and reproductive organs) as well as the affected epidermis...
August 1, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28591585/tcrd-rearrangement-redirects-a-processive-tcra-recombination-program-to-expand-the-tcra-repertoire
#4
Zachary M Carico, Kingshuk Roy Choudhury, Baojun Zhang, Yuan Zhuang, Michael S Krangel
Adaptive immunity depends on diverse T cell receptor repertoires generated by variable, diversity, and joining (V[D]J) recombination. Here, we define the principles by which combinatorial diversity is generated in the murine Tcra repertoire. Tcra and Tcrd gene segments share the Tcra-Tcrd locus, with interspersed Vα and Vδ segments undergoing Vδ-Dδ-Jδ rearrangement in CD4(-)CD8(-) thymocytes and then multiple rounds of Vα-Jα rearrangement in CD4(+)CD8(+) thymocytes. We document stepwise, highly coordinated proximal-to-distal progressions of Vα and Jα use on individual Tcra alleles, limiting combinatorial diversity...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28212502/a-new-mechanism-shapes-the-na%C3%A3-ve-cd8-t-cell-repertoire-the-selection-for-full-diversity
#5
Pedro Gonçalves, Marco Ferrarini, Carmen Molina-Paris, Grant Lythe, Florence Vasseur, Annik Lim, Benedita Rocha, Orly Azogui
During thymic T cell differentiation, TCR repertoires are shaped by negative, positive and agonist selection. In the thymus and in the periphery, repertoires are also shaped by strong inter-clonal and intra-clonal competition to survive death by neglect. Understanding the impact of these events on the T cell repertoire requires direct evaluation of TCR expression in peripheral naïve T cells. Several studies have evaluated TCR diversity, with contradictory results. Some of these studies had intrinsic technical limitations since they used material obtained from T cell pools, preventing the direct evaluation of clonal sizes...
May 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28093446/tumor-infiltrating-merkel-cell-polyomavirus-specific-t-cells-are-diverse-and-associated-with-improved-patient-survival
#6
Natalie J Miller, Candice D Church, Lichun Dong, David Crispin, Matthew P Fitzgibbon, Kristina Lachance, Lichen Jing, Michi Shinohara, Ioannis Gavvovidis, Gerald Willimsky, Martin McIntosh, Thomas Blankenstein, David M Koelle, Paul Nghiem
Tumor-infiltrating CD8(+) T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8(+) T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome. HLA-A*02:01/KLL tetramer(+) CD8(+) T cells from MCC patient peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) were isolated via flow cytometry...
February 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/27935141/evolution-of-a-multi-step-phosphorelay-signal-transduction-system-in-ensifer-recruitment-of-the-sigma-factor-rpon-and-a-novel-enhancer-binding-protein-triggers-acid-activated-gene-expression
#7
Rui Tian, Stephan Heiden, Wan A M Osman, Julie K Ardley, Euan K James, Margaret M Gollagher, Ravi Tiwari, Rekha Seshadri, Nikos C Kyrpides, Wayne G Reeve
Most Ensifer strains are comparatively acid sensitive, compromising their persistence in low pH soils. In the acid-tolerant strain Ensifer medicae WSM419, the acid-activated expression of lpiA is essential for enhancing survival in lethal acidic conditions. Here we characterise a multi-step phosphorelay signal transduction pathway consisting of TcsA, TcrA, FsrR, RpoN and its cognate enhancer-binding protein EbpA, which is required for the induction of lpiA and the downstream acvB gene. The fsrR, tcrA, tcsA and rpoN genes were constitutively expressed, whereas lpiA and acvB were strongly acid-induced...
December 9, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27773811/prevalence-and-impact-of-chronic-endometritis-in-patients-with-intrauterine-adhesions-a-prospective-cohort-study
#8
Yuqing Chen, Lixiang Liu, Yuanna Luo, Minghui Chen, Yang Huan, Ruili Fang
STUDY OBJECTIVE: To evaluate the prevalence and impact of chronic endometritis (CE) in patients with intrauterine adhesions (IUAs). DESIGN: Prospective cohort study (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: Eighty-two women with moderate to severe IUAs. INTERVENTIONS: Transcervical resection of adhesions (TCRA) and endometrial biopsy were performed in all patients...
January 1, 2017: Journal of Minimally Invasive Gynecology
https://www.readbyqxmd.com/read/27760308/evaluation-of-a-synthetic-peptide-from-the-taenia-saginata-18kda-surface-secreted-oncospheral-adhesion-protein-for-serological-diagnosis-of-bovine-cysticercosis
#9
Rafaella Paola Meneguete Guimarães-Peixoto, Paulo Sérgio Arruda Pinto, Marcus Rebouças Santos, Marcelo Depólo Polêto, Letícia Ferreira Silva, Abelardo Silva-Júnior
Bovine cysticercosis is a zoonotic infection widely spread throughout Brazil, creating a burden on hygiene maintenance and the economy. Diagnosis of cysticercosis usually relies on post mortem inspection of carcasses in slaughterhouses. This detection method provides only low sensitivity. Recent advancements have improved the performance of serologic tests, such as ELISA, providing greater sensitivity and specificity. The objective of the current study was to identify and evaluate a synthetic peptide derived from the Taenia saginata 18kDa oncospheric surface protein for the diagnosis of bovine cysticercosis in ELISA...
December 2016: Acta Tropica
https://www.readbyqxmd.com/read/27613698/an-ectopic-ctcf-binding-element-inhibits-tcrd-rearrangement-by-limiting-contact-between-v%C3%AE-and-d%C3%AE-gene-segments
#10
Liang Chen, Lijuan Zhao, Frederick W Alt, Michael S Krangel
Chromatin looping mediated by the CCCTC binding factor (CTCF) regulates V(D)J recombination at Ag receptor loci. CTCF-mediated looping can influence recombination signal sequence (RSS) accessibility by regulating enhancer activation of germline promoters. CTCF-mediated looping has also been shown to limit directional tracking of the RAG recombinase along chromatin, and to regulate long-distance interactions between RSSs, independent of the RAG recombinase. However, in all prior instances in which CTCF-mediated looping was shown to influence V(D)J recombination, it was not possible to fully resolve the relative contributions to the V(D)J recombination phenotype of changes in accessibility, RAG tracking, and RAG-independent long-distance interactions...
October 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27542204/nucks1-synergizes-with-trp53-to-promote-radiation-lymphomagenesis-in-mice
#11
Yangbo Yue, Stanley G Leung, Yueyong Liu, Yurong Huang, Kirsten Grundt, Anne-Carine Østvold, Kuang-Yu Jen, David Schild, Jian-Hua Mao, Claudia Wiese
NUCKS1 is a 27 kD vertebrate-specific protein, with a role in the DNA damage response. Here, we show that after 4 Gy total-body X-irradiation, Trp53+/- Nucks1+/- mice more rapidly developed tumors, particularly thymic lymphoma (TL), than Trp53+/- mice. TLs in both cohorts showed loss of heterozygosity (LOH) of the Trp53+ allele in essentially all cases. In contrast, LOH of the Nucks1+ allele was rare. Nucks1 expression correlated well with Nucks1 gene dosage in normal thymi, but was increased in the majority of TLs from Trp53+/- Nucks1+/- mice, suggesting that elevated Nucks1 message may be associated with progression towards malignancy in vivo...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27500935/disturbance-in-the-mucosa-associated-commensal-bacteria-is-associated-with-the-exacerbation-of-chronic-colitis-by-repeated-psychological-stress-is-that-the-new-target-of-probiotics
#12
Sohei Arase, Yohei Watanabe, Hiromi Setoyama, Noriko Nagaoka, Mitsuhisa Kawai, Satoshi Matsumoto
Psychological stress can exacerbate inflammatory bowel disease. However, the mechanisms underlying how psychological stress affects gut inflammation remain unclear. Here, we focused on the relationship between changes in the microbial community of mucosa-associated commensal bacteria (MACB) and mucosal immune responses induced by chronic psychological stress in a murine model of ulcerative colitis. Furthermore, we examined the effect of probiotic treatment on exacerbated colitis and MACB composition changes induced by chronic psychological stress...
2016: PloS One
https://www.readbyqxmd.com/read/27354337/tumor-and-neoantigen-reactive-t-cell-receptors-can-be-identified-based-on-their-frequency-in-fresh-tumor
#13
Anna Pasetto, Alena Gros, Paul F Robbins, Drew C Deniger, Todd D Prickett, Rodrigo Matus-Nicodemos, Daniel C Douek, Bryan Howie, Harlan Robins, Maria R Parkhurst, Jared Gartner, Katarzyna Trebska-McGowan, Jessica S Crystal, Steven A Rosenberg
Adoptive transfer of T cells with engineered T-cell receptor (TCR) genes that target tumor-specific antigens can mediate cancer regression. Accumulating evidence suggests that the clinical success of many immunotherapies is mediated by T cells targeting mutated neoantigens unique to the patient. We hypothesized that the most frequent TCR clonotypes infiltrating the tumor were reactive against tumor antigens. To test this hypothesis, we developed a multistep strategy that involved TCRB deep sequencing of the CD8(+)PD-1(+) T-cell subset, matching of TCRA-TCRB pairs by pairSEQ and single-cell RT-PCR, followed by testing of the TCRs for tumor-antigen specificity...
September 2, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27133966/characterization-of-the-gilthead-seabream-sparus-aurata-l-immune-response-under-a-natural-lymphocystis-disease-virus-outbreak
#14
H Cordero, A Cuesta, J Meseguer, M A Esteban
Lymphocystis or lymphocystis disease virus (LCDV) is distributed worldwide and affects many fresh and marine water fish species. LCDV is commonly found in aquaria fish species but also in farmed fish species, among them the gilthead seabream (Sparus aurata L.). The immune status of gilthead seabream (S. aurata) specimens under a natural outbreak of LCDV was studied. The replication of the virus was demonstrated in infected fish, but not in control fish. The results showed decreased total serum IgM levels and increased innate cellular immune response (peroxidase and respiratory burst activities) of head kidney leucocytes in LCDV-infected fish, compared to the values obtained in uninfected specimens...
December 2016: Journal of Fish Diseases
https://www.readbyqxmd.com/read/26982384/effectiveness-of-estrogen-treatment-before-transcervical-resection-of-adhesions-on-moderate-and-severe-uterine-adhesion-patients
#15
Ai-Zhen Liu, Hong-Guo Zhao, Ying Gao, Ming Liu, Bao-Zhi Guo
Intrauterine adhesion (IUA), also known as Asherman's syndrome, is a common disease for among women. The extent of adhesion and pre-surgery hormone therapy greatly affects the function of uterine cavity. This current study investigates the association of different doses of estrogen before transcervical resection of adhesions (TCRA) surgery and clinical outcome in serious IUA. About 120 newly diagnostic serious IUA patients who underwent TCRA were randomly divided into three study groups: Estradiol valerate (progynova) 3 or 9 mg per diet before surgery and the control group...
September 2016: Gynecological Endocrinology
https://www.readbyqxmd.com/read/26899003/-clinical-evaluation-of-amniontic-products-after-transcervical-resection-of-intensive-degree-of-intrauterine-adhesions
#16
RANDOMIZED CONTROLLED TRIAL
X Wang, H Duan
OBJECTIVE: To evaluate the effect of amniotic products after transcervical resection of uterine adhesions (TCRA). METHODS: This study was carried out in 57 patients with intensive degree of intrauterine adhesions (IUA) who had been treated by TCRA between Jun. 2013 to Jun. 2014. These patients were devided into two groups randomly. In group amnion, 29 patients were placed amniontic scaffold balloon after TCRA; in group balloon, 28 patients were placed Foley's balloon after TCRA...
January 2016: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/26872611/mapk1-erk2-as-novel-target-genes-for-pain-in-head-and-neck-cancer-patients
#17
Cielito C Reyes-Gibby, Jian Wang, Mary Rose T Silvas, Robert Yu, Sai-Ching J Yeung, Sanjay Shete
BACKGROUND: Genetic susceptibility plays an important role in the risk of developing pain in individuals with cancer. As a complex trait, multiple genes underlie this susceptibility. We used gene network analyses to identify novel target genes associated with pain in patients newly diagnosed with squamous cell carcinoma of the head and neck (HNSCC). RESULTS: We first identified 36 cancer pain-related genes (i.e., focus genes) from 36 publications based on a literature search...
February 13, 2016: BMC Genetics
https://www.readbyqxmd.com/read/26810224/extensive-cd4-and-cd8-t-cell-cross-reactivity-between-alphaherpesviruses
#18
Lichen Jing, Kerry J Laing, Lichun Dong, Ronnie M Russell, Russell S Barlow, Juergen G Haas, Meena S Ramchandani, Christine Johnston, Soren Buus, Alec J Redwood, Katie D White, Simon A Mallal, Elizabeth J Phillips, Christine M Posavad, Anna Wald, David M Koelle
The Alphaherpesvirinae subfamily includes HSV types 1 and 2 and the sequence-divergent pathogen varicella zoster virus (VZV). T cells, controlled by TCR and HLA molecules that tolerate limited epitope amino acid variation, might cross-react between these microbes. We show that memory PBMC expansion with either HSV or VZV enriches for CD4 T cell lines that recognize the other agent at the whole-virus, protein, and peptide levels, consistent with bidirectional cross-reactivity. HSV-specific CD4 T cells recovered from HSV-seronegative persons can be explained, in part, by such VZV cross-reactivity...
March 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/26493028/genetic-characterization-of-t-pll-reveals-two-major-biologic-subgroups-and-jak3-mutations-as-prognostic-marker
#19
Anna Stengel, Wolfgang Kern, Melanie Zenger, Karolína Perglerová, Susanne Schnittger, Torsten Haferlach, Claudia Haferlach
T-cell prolymphocytic leukemia (T-PLL) is a rare post-thymic T-cell neoplasm with aggressive clinical course and short overall survival. So far, due to the rareness of this disease, genetic data are available only from individual cases or small cohorts. In our study, we aimed at performing a comprehensive cytogenetic and molecular genetic characterization of T-PLL comprising the largest cohort of patients with T-PLL analyzed so far, including correlations between the respective markers and their impact on prognosis...
January 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/26290413/high-throughput-pairing-of-t-cell-receptor-%C3%AE-and-%C3%AE-sequences
#20
Bryan Howie, Anna M Sherwood, Ashley D Berkebile, Jan Berka, Ryan O Emerson, David W Williamson, Ilan Kirsch, Marissa Vignali, Mark J Rieder, Christopher S Carlson, Harlan S Robins
The T cell receptor (TCR) protein is a heterodimer composed of an α chain and a β chain. TCR genes undergo somatic DNA rearrangements to generate the diversity of T cell binding specificities needed for effective immunity. Recently, high-throughput immunosequencing methods have been developed to profile the TCR α (TCRA) and TCR β (TCRB) repertoires. However, these methods cannot determine which TCRA and TCRB chains combine to form a specific TCR, which is essential for many functional and therapeutic applications...
August 19, 2015: Science Translational Medicine
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