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Immune repertoire sequencing

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https://www.readbyqxmd.com/read/28107438/first-insights-into-the-subterranean-crustacean-bathynellacea-transcriptome-transcriptionally-reduced-opsin-repertoire-and-evidence-of-conserved-homeostasis-regulatory-mechanisms
#1
Bo-Mi Kim, Seunghyun Kang, Do-Hwan Ahn, Jin-Hyoung Kim, Inhye Ahn, Chi-Woo Lee, Joo-Lae Cho, Gi-Sik Min, Hyun Park
Bathynellacea (Crustacea, Syncarida, Parabathynellidae) are subterranean aquatic crustaceans that typically inhabit freshwater interstitial spaces (e.g., groundwater) and are occasionally found in caves and even hot springs. In this study, we sequenced the whole transcriptome of Allobathynella bangokensis using RNA-seq. De novo sequence assembly produced 74,866 contigs including 28,934 BLAST hits. Overall, the gene sequences were most similar to those of the waterflea Daphnia pulex. In the A. bangokensis transcriptome, no opsin or related sequences were identified, and no contig aligned to the crustacean visual opsins and non-visual opsins (i...
2017: PloS One
https://www.readbyqxmd.com/read/28096374/phylogenetic-analysis-of-the-human-antibody-repertoire-reveals-quantitative-signatures-of-immune-senescence-and-aging
#2
Charles F A de Bourcy, Cesar J Lopez Angel, Christopher Vollmers, Cornelia L Dekker, Mark M Davis, Stephen R Quake
The elderly have reduced humoral immunity, as manifested by increased susceptibility to infections and impaired vaccine responses. To investigate the effects of aging on B-cell receptor (BCR) repertoire evolution during an immunological challenge, we used a phylogenetic distance metric to analyze Ig heavy-chain transcript sequences in both young and elderly individuals before and after influenza vaccination. We determined that BCR repertoires become increasingly specialized over a span of decades, but less plastic...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095438/vh1-family-immunoglobulin-repertoire-sequencing-after-allogeneic-hematopoietic-stem-cell-transplantation
#3
Maya K Sethi, Felicitas Thol, Michael Stadler, Michael Heuser, Arnold Ganser, Christian Koenecke, Oliver Pabst
After allogeneic hematopoietic stem cell transplantation (HSCT), recovery of humoral immunity is essential to protect from life-threatening infections. However, monitoring the humoral immune system after transplantation with standard techniques in the clinical routine is imprecise. Here, we performed sequencing of mononuclear bone marrow cells to characterize the VH1-repertoire of switched B cells of healthy volunteers and patients undergoing HSCT. Analysis of healthy bone marrow donors and patients showed virtually no clonally related sequences between individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28093524/age-associated-b-cells-express-a-diverse-repertoire-of-vh-and-v%C3%AE%C2%BA-genes-with-somatic-hypermutation
#4
Lisa M Russell Knode, Martin S Naradikian, Arpita Myles, Jean L Scholz, Yi Hao, Danya Liu, Mandy L Ford, John W Tobias, Michael P Cancro, Patricia J Gearhart
The origin and nature of age-associated B cells (ABCs) in mice are poorly understood. In this article, we show that their emergence required MHC class II and CD40/CD40L interactions. Young donor B cells were adoptively transferred into congenic recipients and allowed to remain for 1 mo in the absence of external Ag. B cells expressing the T-bet transcription factor, a marker for ABCs, were generated after multiple cell divisions from C57BL/6 donors but not from MHC class II- or CD40-deficient donors. Furthermore, old CD154 (CD40L)-deficient mice did not accrue ABCs, confirming that they arise primarily through T-dependent interactions...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28091735/comprehensive-assessment-of-peripheral-blood-tcr%C3%AE-repertoire-in-infectious-mononucleosis-and-chronic-active-ebv-infection-patients
#5
Shenglin Liu, Qian Zhang, Dongli Huang, Wenli Zhang, Fengluan Zhong, Jia Feng, Xueru Chen, Qingxiang Meng, Xiaofan Chen, Wei Zhang, Hongyu Zhang
Epstein-Barr virus (EBV) primary infection is usually asymptomatic, but it sometimes progresses to infectious mononucleosis (IM). Occasionally, some people develop chronic active EBV infection (CAEBV) with underlying immunodeficiency, which belongs to a continuous spectrum of EBV-associated lymphoproliferative disorders (EBV(+) LPD) with heterogeneous clinical presentations and high mortality. It has been well established that T cell-mediated immune response plays a critical role in the disease evolution of EBV infection...
January 14, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28088364/antibodies-from-novel-repertoires-to-defining-and-refining-the-structure-of-biologically-important-targets
#6
REVIEW
Paul J Conroy, Ruby H P Law, Tom Caradoc-Davies, James C Whisstock
Antibodies represent a highly successful class of molecules that bind a wide-range of targets in therapeutic-, diagnostic- and research-based applications. The antibody repertoire is composed of the building blocks required to develop an effective adaptive immune response against foreign insults. A number of species have developed novel genetic and structural mechanisms from which they derive these antibody repertoires, however, traditionally antibodies are derived from human, and rodent sources. Due to their high-value therapeutic, diagnostic, biotechnological and research applications, much innovation has resulted in techniques and approaches to isolate novel antibodies...
January 11, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28077600/ibrutinib-therapy-increases-t-cell-repertoire-diversity-in-patients-with-chronic-lymphocytic-leukemia
#7
Qingsong Yin, Mariela Sivina, Harlan Robins, Erik Yusko, Marissa Vignali, Susan O'Brien, Michael J Keating, Alessandra Ferrajoli, Zeev Estrov, Nitin Jain, William G Wierda, Jan A Burger
The Bruton's tyrosine kinase inhibitor ibrutinib is a highly effective, new targeted therapy for chronic lymphocytic leukemia (CLL) that thwarts leukemia cell survival, growth, and tissue homing. The effects of ibrutinib treatment on the T cell compartment, which is clonally expanded and thought to support the growth of malignant B cells in CLL, are not fully characterized. Using next-generation sequencing technology, we characterized the diversity of TCRβ-chains in peripheral blood T cells from 15 CLL patients before and after 1 y of ibrutinib therapy...
January 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28077404/high-throughput-sequencing-of-the-t-cell-receptor-repertoire-pitfalls-and-opportunities
#8
James M Heather, Mazlina Ismail, Theres Oakes, Benny Chain
T-cell specificity is determined by the T-cell receptor, a heterodimeric protein coded for by an extremely diverse set of genes produced by imprecise somatic gene recombination. Massively parallel high-throughput sequencing allows millions of different T-cell receptor genes to be characterized from a single sample of blood or tissue. However, the extraordinary heterogeneity of the immune repertoire poses significant challenges for subsequent analysis of the data. We outline the major steps in processing of repertoire data, considering low-level processing of raw sequence files and high-level algorithms, which seek to extract biological or pathological information...
January 10, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28074285/t-cell-receptor-repertoire-usage-in-cancer-as-a-surrogate-marker-for-immune-responses
#9
REVIEW
David Schrama, Cathrin Ritter, Jürgen C Becker
Characterizing the interaction of cancer cells with the host adaptive immune system is critical for understanding tumor immunology and the modus operandi of immunotherapeutic interventions to treat cancer. As the key cellular effectors of adaptive immunity, T cells are endowed with specialized receptors (the T cell receptor; TCR), to recognize and to eliminate cancer cells. The diversity of the TCR repertoire results from specialized genetic diversification mechanisms that generate an incredible variability allowing recognizing extensive collections of antigens...
January 10, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28073756/feature-selection-using-a-one-dimensional-na%C3%A3-ve-bayes-classifier-increases-the-accuracy-of-support-vector-machine-classification-of-cdr3-repertoires
#10
Mattia Cinelli, Yuxin Sun, Katharine Best, James M Heather, Shlomit Reich-Zeliger, Eric Shifrut, Nir Friedman, John Shawe-Taylor, Benny Chain
MOTIVATION: Somatic DNA recombination, the hallmark of vertebrate adaptive immunity, has the potential to generate a vast diversity of antigen receptor sequences. How this diversity captures antigen specificity remains incompletely understood. In this study we use high throughput sequencing to compare the global changes in T cell receptor β chain complementarity determining region 3 (CDR3β) sequences following immunization with ovalbumin administered with complete Freund's adjuvant (CFA) or CFA alone...
January 10, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28057863/mutational-landscape-of-antibody-variable-domains-reveals-a-switch-modulating-the-interdomain-conformational-dynamics-and-antigen-binding
#11
Patrick Koenig, Chingwei V Lee, Benjamin T Walters, Vasantharajan Janakiraman, Jeremy Stinson, Thomas W Patapoff, Germaine Fuh
Somatic mutations within the antibody variable domains are critical to the immense capacity of the immune repertoire. Here, via a deep mutational scan, we dissect how mutations at all positions of the variable domains of a high-affinity anti-VEGF antibody G6.31 impact its antigen-binding function. The resulting mutational landscape demonstrates that large portions of antibody variable domain positions are open to mutation, and that beneficial mutations can be found throughout the variable domains. We determine the role of one antigen-distal light chain position 83, demonstrating that mutation at this site optimizes both antigen affinity and thermostability by modulating the interdomain conformational dynamics of the antigen-binding fragment...
January 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28055305/generation-of-a-highly-diverse-panel-of-antagonistic-chicken-monoclonal-antibodies-against-the-gip-receptor
#12
Jennifer D Könitzer, Shreya Pramanick, Qi Pan, Robert Augustin, Sebastian Bandholtz, William Harriman, Shelley Izquierdo
Raising functional antibodies against G protein-coupled receptors (GPCRs) is challenging due to their low density expression, instability in the absence of the cell membrane's lipid bilayer and frequently short extracellular domains that can serve as antigens. In addition, a particular therapeutic concept may require an antibody to not just bind the receptor, but also act as a functional receptor agonist or antagonist. Antagonizing the glucose-dependent insulinotropic polypeptide (GIP) receptor may open up new therapeutic modalities in the treatment of diabetes and obesity...
January 5, 2017: MAbs
https://www.readbyqxmd.com/read/28053320/direct-measurement-of-b-cell-receptor-repertoire-s-composition-and-variation-in-systemic-lupus-erythematosus
#13
S Liu, X L Hou, W G Sui, Q J Lu, Y L Hu, Y Dai
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is known to be associated with polyclonal B-cell hyper-reactivity. B-cell receptor (BCR) has a central role in B-cell development, activation, survival and apoptosis, and thus is a critical component of the regulation of both protective and autoreactive B cells. In this study, we applied multiplex PCR and Illumina high-throughput sequencing to study the composition and variation of the BCRs in peripheral blood mononuclear cells from SLE patients and healthy donors (NC)...
January 5, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28039161/the-different-t-cell-receptor-repertoires-in-breast-cancer-tumors-draining-lymph-nodes-and-adjacent-tissues
#14
Ting Wang, Changxi Wang, Jinghua Wu, Chenyang He, Wei Zhang, Jiayun Liu, Ruifang Zhang, Yonggang Lv, Yongping Li, Xiaojing Zeng, Hongzhi Cao, Xiuqing Zhang, Xun Xu, Chen Huang, Ling Wang, Xiao Liu
T lymphocytes infiltrate the microenvironment of breast cancer (BC) tumors and play a pivotal role in tumor immune surveillance. Relationships between the T-cell receptors (TCRs) borne by T cells within tumors, in the surrounding tissues, and in draining lymph nodes are largely unexplored in human breast cancer. Consequently, information about the relative extent of possible T-cell exchange between these tissues is also lacking. Here we have analyzed the TCR repertoire of T cells using multiplex PCR and high throughput sequencing of the TCRβ chain in the tissues of tumor, adjacent nontumor, and axillary lymph-nodes of breast cancer patients...
December 30, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/28038935/defense-peptide-repertoire-of-stellaria-media-predicted-by-high-throughput-next-generation-sequencing
#15
Anna A Slavokhotova, Andrey A Shelenkov, Tatyana V Korostyleva, Eugene A Rogozhin, Nataliya V Melnikova, Anna V Kudryavtseva, Tatyana I Odintsova
Being perfectly adapted to diverse environments, chickweed (Stellaria media (L.) Vill), a ubiquitous garden weed, grows widely in Europe and North America. As opposed to the model plants, many weeds, and S. media in particular, have been poorly studied, although they are likely to contain promising components of immunity and novel resistance genes. In this study, for the first time RNA-seq analysis of healthy and infected with Fusarium oxysporum chickweed seedlings, as well as de novo transcriptome assembly and annotation, are presented...
December 27, 2016: Biochimie
https://www.readbyqxmd.com/read/28024918/t-cell-repertoire-diversity-is-decreased-in-type-1-diabetes-patients
#16
Yin Tong, Zhoufang Li, Hua Zhang, Ligang Xia, Meng Zhang, Ying Xu, Zhanhui Wang, Michael W Deem, Xiaojuan Sun, Jiankui He
Type 1 diabetes mellitus (T1D) is an immune-mediated disease. The autoreactive T cells in T1D patients attack and destroy their own pancreatic cells. In order to systematically investigate the potential autoreactive T cell receptors (TCRs), we used a high-throughput immune repertoire sequencing technique to profile the spectrum of TCRs in individual T1D patients and controls. We sequenced the T cell repertoire of nine T1D patients, four type 2 diabetes (T2D) patients, and six nondiabetic controls. The diversity of the T cell repertoire in T1D patients was significantly decreased in comparison with T2D patients (P=7...
December 2016: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28005056/new-crispr-cas-systems-from-uncultivated-microbes
#17
David Burstein, Lucas B Harrington, Steven C Strutt, Alexander J Probst, Karthik Anantharaman, Brian C Thomas, Jennifer A Doudna, Jillian F Banfield
CRISPR-Cas systems provide microbes with adaptive immunity by employing short sequences, termed spacers, that guide Cas proteins to cleave foreign DNA(1,2). Class 2 CRISPR-Cas systems are streamlined versions in which a single Cas protein bound to RNA recognizes and cleaves targeted sequences(3,4). The programmable nature of these minimal systems has enabled their repurposing as a versatile technology that is broadly revolutionizing biological and clinical research(5). However, current CRISPR-Cas technologies are based solely on systems from isolated bacteria, leaving untapped the vast majority of enzymes from organisms that have not been cultured...
December 22, 2016: Nature
https://www.readbyqxmd.com/read/28000661/temporal-stability-and-molecular-persistence-of-the-bone-marrow-plasma-cell-antibody-repertoire
#18
Gabriel C Wu, Nai-Kong V Cheung, George Georgiou, Edward M Marcotte, Gregory C Ippolito
Plasma cells in human bone marrow (BM) are thought to be responsible for sustaining lifelong immunity, but its underlying basis is controversial. Here we use high-throughput sequence analysis of the same individual across 6.5 years to show that the BM plasma cell immunoglobulin heavy chain repertoire is remarkably stable over time. We find a nearly static bias in individual and combinatorial gene usage across time. Analysis of a second donor corroborates these observations. We also report the persistence of numerous BM plasma cell clonotypes (∼2%) identifiable at all points assayed across 6...
December 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27942581/b-cell-repertoire-expansion-occurs-in-meningeal-ectopic-lymphoid-tissue
#19
Klaus Lehmann-Horn, Sheng-Zhi Wang, Sharon A Sagan, Scott S Zamvil, H-Christian von Büdingen
Ectopic lymphoid tissues (ELT) can be found in multiple sclerosis (MS) and other organ-specific inflammatory conditions. Whether ELT in the meninges of central nervous system (CNS) autoimmune disease exhibit local germinal center (GC) activity remains unknown. In an experimental autoimmune encephalomyelitis model of CNS autoimmunity, we found activation-induced cytidine deaminase, a GC-defining enzyme, in meningeal ELT (mELT) densely populated by B and T cells. To determine GC activity in mELT, we excised meningeal lymphoid aggregates using laser capture microscopy and evaluated B cell repertoires in mELT and secondary lymphoid organs by next-generation immune repertoire sequencing...
December 8, 2016: JCI Insight
https://www.readbyqxmd.com/read/27941777/gvl-effects-in-t-prolymphocytic-leukemia-evidence-from-mrd-kinetics-and-tcr-repertoire-analyses
#20
L Sellner, M Brüggemann, M Schlitt, H Knecht, D Herrmann, T Reigl, A Krejci, V Bystry, N Darzentas, M Rieger, S Dietrich, T Luft, A D Ho, M Kneba, P Dreger
Allogeneic stem cell transplantation (alloSCT) is used for treating patients with T-prolymphocytic leukemia (T-PLL). However, direct evidence of GvL activity in T-PLL is lacking. We correlated minimal residual disease (MRD) kinetics with immune interventions and T-cell receptor (TCR) repertoire diversity alterations in patients after alloSCT for T-PLL. Longitudinal quantitative MRD monitoring was performed by clone-specific real-time PCR of TCR rearrangements (n=7), and TCR repertoire diversity assessment by next-generation sequencing (NGS; n=3) Although post-transplant immunomodulation (immunosuppression tapering or donor lymphocyte infusions) resulted in significant reduction (>1 log) of MRD levels in 7 of 10 occasions, durable MRD clearance was observed in only two patients...
December 12, 2016: Bone Marrow Transplantation
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