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Repertoire Sequencing

Lili Chen, Zhengxiang He, Alina Cornelia Iuga, Sebastião N Martins Filho, Jeremiah J Faith, Jose C Clemente, Madhura Deshpande, Anitha Jayaprakash, Jean-Frederic Colombel, Juan J Lafaille, Ravi Sachidanandam, Glaucia C Furtado, Sergio A Lira
BACKGROUND & AIMS: Several studies have shown that signaling via the interleukin 23 (IL23) receptor is required for development of colitis. We studied the roles of IL23, dietary factors, alterations to the microbiota, and T cells in development and progression of colitis in mice. METHODS: All mice were maintained on lab diet 5053, unless otherwise noted. We generated mice that express IL23 in CX3CR1-positive myeloid cells (R23FR mice) upon cyclic administration of tamoxifen dissolved in diet 2019...
June 14, 2018: Gastroenterology
Aurélie Berland, Jérémie Rosain, Sophie Kaltenbach, Vincent Allain, Nizar Mahlaoui, Isabelle Melki, Alice Fievet, Catherine Dubois d'Enghien, Marie Ouachée-Chardin, Laurence Perrin, Nathalie Auger, Funda Erol Cipe, Andrea Finocchi, Figen Dogu, Felipe Suarez, Despina Moshous, Thierry Leblanc, Alexandre Belot, Claire Fieschi, David Boutboul, Marion Malphettes, Lionel Galicier, Eric Oksenhendler, Stéphane Blanche, Alain Fischer, Patrick Revy, Dominique Stoppa-Lyonnet, Capucine Picard, Jean-Pierre de Villartay
- BACKGROUND: V(D)J recombination ensures the diversity of the adaptive immune system. While its complete defect causes Severe Combined Immunodeficiency (T-B-SCID), its suboptimal activity, is associated with a broad spectrum of immune manifestations such as late onset combined immunodeficiency and autoimmunity. The earliest molecular diagnosis of these patients is required to adopt the best therapy strategy, in particular when it involves myelo-ablative conditioning regimen for hematopoietic stem cell transplantation (HSCT)...
June 12, 2018: Journal of Allergy and Clinical Immunology
Nicolas De Neuter, Esther Bartholomeus, George Elias, Nina Keersmaekers, Arvid Suls, Hilde Jansens, Evelien Smits, Niel Hens, Philippe Beutels, Pierre Van Damme, Geert Mortier, Viggo Van Tendeloo, Kris Laukens, Pieter Meysman, Benson Ogunjimi
Pathogens of past and current infections have been identified directly by means of PCR or indirectly by measuring a specific immune response (e.g., antibody titration). Using a novel approach, Emerson and colleagues showed that the cytomegalovirus serostatus can also be accurately determined by using a T cell receptor repertoire data mining approach. In this study, we have sequenced the CD4+ memory T cell receptor repertoire of a Belgian cohort with known cytomegalovirus serostatus. A random forest classifier was trained on the CMV specific T cell receptor repertoire signature and used to classify individuals in the Belgian cohort...
June 15, 2018: Genes and Immunity
Ryan L Powles, David Redmond, Christos Sotiriou, Sherene Loi, Debora Fumagalli, Paolo Nuciforo, Nadia Harbeck, Evandro de Azambuja, Severine Sarp, Serena Di Cosimo, Jens Huober, Jose Baselga, Martine Piccart-Gebhart, Olivier Elemento, Lajos Pusztai, Christos Hatzis
Importance: Dual anti-HER2 blockade increased the rate of pathologic complete response (pCR) in the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (NeoALTTO) trial, and high immune gene expression was associated with pCR in all treatment arms. So far, no marker has been identified that is specifically associated with the benefit from dual HER2 blockade. Objective: To examine if use of the T-cell β chain variable genes adds to the potential association of immune gene signatures with response to dual HER2 blockade...
June 14, 2018: JAMA Oncology
Giovanna Brancati, Helge Großhans
MicroRNAs often occur in families whose members share an identical 5' terminal 'seed' sequence. The seed is a major determinant of miRNA activity, and family members are thought to act redundantly on target mRNAs with perfect seed matches, i.e. sequences complementary to the seed. However, recently sequences outside the seed were reported to promote silencing by individual miRNA family members. Here, we examine this concept and the importance of miRNA specificity for the robustness of developmental gene control...
April 20, 2018: Nucleic Acids Research
Tamara Salloum, Elie Nassour, George F Araj, Edmond Abboud, Sima Tokajian
PURPOSE: Burkholderia cenocepacia is among the most common members of the Burkholderia cepacia complex (Bcc) isolated from patients with cystic fibrosis (CF). The factors triggering the high rates of morbidity and mortality in CF patients are not well elucidated. In this study, we aim to highlight the genome diversity of two clinical isolates of B. cenocepacia through comparative genome analysis. METHODOLOGY: The repertoire of virulence factors and resistance genes compared to reference strains J2315 and K56-2 was elucidated...
June 13, 2018: Journal of Medical Microbiology
Ludmila Danilova, Valsamo Anagnostou, Justina X Caushi, John-William Sidhom, Haidan Guo, Hok Yee Chan, Prerna Suri, Ada J Tam, Jiajia Zhang, Margueritta El Asmar, Kristen A Marrone, Jarushka Naidoo, Julie R Brahmer, Patrick M Forde, Alexander S Baras, Leslie Cope, Victor E Velculescu, Drew Pardoll, Franck Housseau, Kellie N Smith
Mutation-associated neoantigens (MANAs) are a target of antitumor T-cell immunity. Sensitive, simple, and standardized assays are needed to assess the repertoire of functional MANA-specific T cells in oncology. Assays analyzing in vitro cytokine production such as ELISpot and intracellular cytokine staining (ICS) have been useful but have limited sensitivity in assessing tumor-specific T-cell responses and do not analyze antigen-specific T-cell repertoires. The FEST (Functional Expansion of Specific T cells) assay described herein integrates TCR sequencing of short-term, peptide-stimulated cultures with a bioinformatic platform to identify antigen-specific clonotypic amplifications...
June 12, 2018: Cancer Immunology Research
Federica Pierini, Tobias L Lenz
The highly polymorphic genes of the major histocompatibility complex (MHC) play a key role in adaptive immunity. Divergent allele advantage, a mechanism of balancing selection, is proposed to contribute to their exceptional polymorphism. It assumes that MHC genotypes with more divergent alleles allow for broader antigen-presentation to immune effector cells, by that increasing immunocompetence. However, the direct correlation between pairwise sequence divergence and the corresponding repertoire of bound peptides has not been studied systematically across different MHC genes...
June 8, 2018: Molecular Biology and Evolution
Benoit Castrec, Cyril Dian, Sarah Ciccone, Coralie L Ebert, Willy V Bienvenut, Jean-Pierre Le Caer, Jean-Marc Steyaert, Carmela Giglione, Thierry Meinnel
An organism's entire protein modification repertoire has yet to be comprehensively mapped. N-myristoylation (MYR) is a crucial eukaryotic N-terminal protein modification. Here we mapped complete Homo sapiens and Arabidopsis thaliana myristoylomes. The crystal structures of human modifier NMT1 complexed with reactive and nonreactive target-mimicking peptide ligands revealed unexpected binding clefts and a modifier recognition pattern. This information allowed integrated mapping of myristoylomes using peptide macroarrays, dedicated prediction algorithms, and in vivo mass spectrometry...
June 11, 2018: Nature Chemical Biology
Anne Musters, Paul L Klarenbeek, Marieke E Doorenspleet, Giulia Balzaretti, Rebecca E E Esveldt, Barbera D C van Schaik, Aldo Jongejan, Sander W Tas, Antoine H C van Kampen, Frank Baas, Niek de Vries
Genetic and immunological evidence clearly points to a role for T cells in the pathogenesis of rheumatoid arthritis (RA). Selective targeting of such disease-associated T cell clones might be highly effective while having few side effects. However, such selective targeting may only be feasible if the same T cell clones dominate the immune response at different sites of inflammation. We leveraged high-throughput technology to quantitatively assess whether different T cell clones dominate the inflammatory infiltrate at various sites of inflammation in this prototypic autoimmune disease...
June 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Fengyu She, Peng Teng, Alfredo Peguero-Tejada, Minghui Wang, Ning Ma, Timothy Odom, Mi Zhou, Erald Gjonaj, Lukasz Wojtas, Arjan van der Vaart, Jianfeng Cai
Development of peptidomimetic helical foldamers with a wide repertoire of functions is of significant interest. Herein, for the first time, we report the X-ray crystal structures of a series of homogeneous L-sulfono-γ-AA foldamers, and elucidate their folding conformation at the atomic level. Single crystal X-ray crystallography reveals that this class of oligomers fold into unprecedented dragon-boat-shaped and surprisingly unexpected left-handed helices, which are stabilized by the 14-hydrogen bonding pattern unanimously present in the sequences...
June 11, 2018: Angewandte Chemie
Alexandre Bueno Santos, Patrícia Silva Costa, Anderson Oliveira do Carmo, Gabriel da Rocha Fernandes, Larissa Lopes Silva Scholte, Jeronimo Ruiz, Evanguedes Kalapothakis, Edmar Chartone-Souza, Andréa Maria Amaral Nascimento
Members of the genus Chromobacterium have been isolated from geographically diverse ecosystems and exhibit considerable metabolic flexibility, as well as biotechnological and pathogenic properties in some species. This study reports the draft assembly and detailed sequence analysis of Chromobacterium amazonense strain 56AF. The de novo-assembled genome is 4,556,707 bp in size and contains 4294 protein-coding and 95 RNA genes, including 88 tRNA, six rRNA, and one tmRNA operon. A repertoire of genes implicated in virulence, for example, hemolysin, hemolytic enterotoxins, colicin V, lytic proteins, and Nudix hydrolases, is present...
2018: International Journal of Genomics
Børre Fevang, Unn Merete Fagerli, Hanne Sorte, Harald Aarset, Håkon Hov, Marit Langmyr, Thomas Morten Keil, Ellen Bjørge, Pål Aukrust, Asbjørg Stray-Pedersen, Tobias Gedde-Dahl
The nuclease Artemis is essential for the development of T-cell and B-cell receptors and repair of DNA double-strand breaks, and a loss of expression or function will lead to a radiosensitive severe combined immunodeficiency with no functional T-cells or B-cells (T-B-SCID). Hypomorphic mutations in the Artemis gene can lead to a functional, but reduced, T-cell and B-cell repertoire with a more indolent clinical course called "leaky" SCID. Here, we present the case of a young man who had increasingly aggressive lymphoproliferative skin lesions from 2 years of age which developed into multiple EBV+ B-cell lymphomas, where a hypomorphic mutation in the Artemis gene was found in a diagnostic race against time using whole exome sequencing...
2018: Case Reports in Immunology
Johannes Textor, Anke Fähnrich, Martin Meinhardt, Cornelia Tune, Sebastian Klein, Rene Pagel, Peter König, Kathrin Kalies, Jürgen Westermann
Immunological differences between hosts, such as diverse TCR repertoires, are widely credited for reducing the risk of pathogen spread and adaptation in a population. Within-host immunological diversity might likewise be important for robust pathogen control, but to what extent naive TCR repertoires differ across different locations in the same host is unclear. T cell zones (TCZs) in secondary lymphoid organs provide secluded microenvironmental niches. By harboring distinct TCRs, such niches could enhance within-host immunological diversity...
June 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Rui Wu, Lina Duan, Jose Pruneda-Paz, Dong-Ha Oh, Michael P Pound, Steve A Kay, Jose R Dinneny
The water stress-associated hormone abscisic acid (ABA) acts through a well-defined signal transduction cascade to mediate downstream transcriptional events important for acclimation to stress. Although ABA signaling is known to function in specific tissues to regulate root growth, little is understood regarding the spatial pattern of ABA-mediated transcriptional regulation. Here we describe the construction and evaluation of an ABSCISIC ACID RESPONSIVE ELEMENT (ABRE)-based synthetic promoter reporter that reveals the transcriptional response of tissues to different levels of exogenous ABA and stresses...
June 8, 2018: Plant Physiology
Carmen Oeo-Santos, Salvador Mas, Sara Benedé, María López-Lucendo, Joaquín Quiralte, Miguel Blanca, Cristobalina Mayorga, Mayte Villalba, Rodrigo Barderas
The allergenic non-specific lipid transfer protein Ole e 7 from olive pollen is a major allergen associated with severe symptoms in areas with high olive pollen levels. Despite its clinical importance, its cloning and recombinant production has been unable by classical approaches. This study aimed at determining by mass-spectrometry based proteomics its complete amino acid sequence for its subsequent expression and characterization. To this end, the natural protein was in-2D-gel tryptic digested, and CID and HCD fragmentation spectra obtained by nLC-MS/MS analyzed using PEAKS software...
June 5, 2018: Journal of Proteomics
Maria Nevot, Ana Jordan-Paiz, Glòria Martrus, Cristina Andrés, Damir García-Cehic, Josep Gregori, Sandra Franco, Josep Quer, Miguel Angel Martinez
One unexplored aspect of HIV-1 genetic architecture is how codon choice influences population diversity and evolvability. Here we compared the development of HIV-1 resistance to protease inhibitors (PIs) between wild-type (WT) virus and a synthetic virus (MAX) carrying a codon-pair re-engineered protease sequence including 38 (13%) synonymous mutations. WT and MAX viruses showed indistinguishable replication in MT-4 cells or PBMCs. Both viruses were subjected to serial passages in MT-4 cells with selective pressure from the PIs atazanavir (ATV) and darunavir (DRV)...
June 6, 2018: Journal of Virology
Gonzalo Blanco, Anna Vardi, Anna Puiggros, Andrea Gómez-Llonín, Manuel Muro, María Rodríguez-Rivera, Evangelia Stalika, Eugenia Abella, Eva Gimeno, Manuela López-Sánchez, Alicia Senín, Xavier Calvo, Pau Abrisqueta, Francesc Bosch, Ana Ferrer, Kostas Stamatopoulos, Blanca Espinet
Analysis of the T cell receptor (TR) repertoire of chronic lymphocytic leukemia-like monoclonal B cell lymphocytosis (CLL-like MBL) and early stage CLL is relevant for understanding the dynamic interaction of expanded B cell clones with bystander T cells. Here we profiled the T cell receptor β chain (TRB) repertoire of the CD4+ and CD8+ T cell fractions from 16 CLL-like MBL and 13 untreated, Binet stage A/Rai stage 0 CLL patients using subcloning analysis followed by Sanger sequencing. The T cell subpopulations of both MBL and early stage CLL harbored restricted TRB gene repertoire, with CD4+ T cell clonal expansions whose frequency followed the numerical increase of clonal B cells...
2018: Oncoimmunology
Wahiba Chaara, Ariadna Gonzalez-Tort, Laura-Maria Florez, David Klatzmann, Encarnita Mariotti-Ferrandiz, Adrien Six
High-throughput sequencing (HTS) has the potential to decipher the diversity of T cell repertoires and their dynamics during immune responses. Applied to T cell subsets such as T effector and T regulatory cells, it should help identify novel biomarkers of diseases. However, given the extreme diversity of TCR repertoires, understanding how the sequencing conditions, including cell numbers, biological and technical sampling and sequencing depth, impact the experimental outcome is critical to proper use of these data...
2018: Frontiers in Immunology
Anke Fähnrich, Sebastian Klein, Arnauld Sergé, Christin Nyhoegen, Sabrina Kombrink, Steffen Möller, Karsten Keller, Jürgen Westermann, Kathrin Kalies
CD154 is a transmembrane cytokine expressed transiently on activated CD4 T cells upon T-cell receptor (TCR) stimulation that interacts with CD40 on antigen-presenting cells. The signaling via CD154:CD40 is essential for B-cell maturation and germinal center formation and also for the final differentiation of CD4 T cells during T-dependent humoral immune responses. Recent data demonstrate that CD154 is critically involved in the selection of T-cell clones during the negative selection process in the thymus. Whether CD154 signaling influences the TCR repertoire during peripheral T-dependent humoral immune responses has not yet been elucidated...
2018: Frontiers in Immunology
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