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Immune repertoire sequencing

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https://www.readbyqxmd.com/read/27896747/studying-antibody-repertoires-with-next-generation-sequencing
#1
William D Lees, Adrian J Shepherd
Next-generation sequencing is making it possible to study the antibody repertoire of an organism in unprecedented detail, and, by so doing, to characterize its behavior in the response to infection and in pathological conditions such as autoimmunity and cancer. The polymorphic nature of the repertoire poses unique challenges that rule out the use of many commonly used NGS methods and require tradeoffs to be made when considering experimental design.We outline the main contexts in which antibody repertoire analysis has been used, and summarize the key tools that are available...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27896028/the-scavenger-receptor-repertoire-in-six-cnidarian-species-and-its-putative-role-in-cnidarian-dinoflagellate-symbiosis
#2
Emilie F Neubauer, Angela Z Poole, Virginia M Weis, Simon K Davy
Many cnidarians engage in a mutualism with endosymbiotic photosynthetic dinoflagellates that forms the basis of the coral reef ecosystem. Interpartner interaction and regulation includes involvement of the host innate immune system. Basal metazoans, including cnidarians have diverse and complex innate immune repertoires that are just beginning to be described. Scavenger receptors (SR) are a diverse superfamily of innate immunity genes that recognize a broad array of microbial ligands and participate in phagocytosis of invading microbes...
2016: PeerJ
https://www.readbyqxmd.com/read/27894837/cd4-virtual-memory-antigen-inexperienced-t-cells-reside-in-the-na%C3%A3-ve-regulatory-and-memory-t-cell-compartments-at-similar-frequencies-implications-for-autoimmunity
#3
Alina I Marusina, Yoko Ono, Alexander A Merleev, Michiko Shimoda, Hiromi Ogawa, Elizabeth A Wang, Kayo Kondo, Laura Olney, Guillaume Luxardi, Yoshinori Miyamura, Tilahun D Yilma, Itzel Bustos Villalobos, Jennifer W Bergstrom, Daniel G Kronenberg, Athena M Soulika, Iannis E Adamopoulos, Emanual Maverakis
It is widely accepted that central and effector memory CD4(+) T cells originate from naïve T cells after they have encountered their cognate antigen in the setting of appropriate co-stimulation. However, if this were true the diversity of T cell receptor (TCR) sequences within the naïve T cell compartment should be far greater than that of the memory T cell compartment, which is not supported by TCR sequencing data. Here we demonstrate that aged mice with far fewer naïve T cells, respond to the model antigen, hen eggwhite lysozyme (HEL), by utilizing the same TCR sequence as their younger counterparts...
November 25, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27893816/mir-34-modulates-innate-immunity-and-ecdysone-signaling-in-drosophila
#4
Xiao-Peng Xiong, Krishna Kurthkoti, Kung-Yen Chang, Jian-Liang Li, Xingjie Ren, Jian-Quan Ni, Tariq M Rana, Rui Zhou
microRNAs are endogenous small regulatory RNAs that modulate myriad biological processes by repressing target gene expression in a sequence-specific manner. Here we show that the conserved miRNA miR-34 regulates innate immunity and ecdysone signaling in Drosophila. miR-34 over-expression activates antibacterial innate immunity signaling both in cultured cells and in vivo, and flies over-expressing miR-34 display improved survival and pathogen clearance upon Gram-negative bacterial infection; whereas miR-34 knockout animals are defective in antibacterial defense...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27878834/characterization-of-mirnas-involved-in-response-to-poly-i-c-in-porcine-airway-epithelial-cells
#5
L Wang, J K Wang, L X Han, J S Zhuo, X Du, D Liu, X Q Yang
MicroRNAs (miRNA) have been implicated in a variety of pathological conditions including infectious diseases. Knowledge of the miRNAs affected by poly(I:C), a synthetic analog of viral double-stranded RNA, in porcine airway epithelial cells (PAECs) contributes to understanding the mechanisms of swine viral respiratory diseases, which bring enormous economic loss worldwide every year. In this study, we used high throughput sequencing to profile miRNA expression in PAECs treated with poly(I:C) as compared to the untreated control...
November 22, 2016: Animal Genetics
https://www.readbyqxmd.com/read/27867380/impre-an-accurate-and-efficient-software-for-prediction-of-t-and-b-cell-receptor-germline-genes-and-alleles-from-rearranged-repertoire-data
#6
Wei Zhang, I-Ming Wang, Changxi Wang, Liya Lin, Xianghua Chai, Jinghua Wu, Andrew J Bett, Govindarajan Dhanasekaran, Danilo R Casimiro, Xiao Liu
Large-scale study of the properties of T-cell receptor (TCR) and B-cell receptor (BCR) repertoires through next-generation sequencing is providing excellent insights into the understanding of adaptive immune responses. Variable(Diversity)Joining [V(D)J] germline genes and alleles must be characterized in detail to facilitate repertoire analyses. However, most species do not have well-characterized TCR/BCR germline genes because of their high homology. Also, more germline alleles are required for humans and other species, which limits the capacity for studying immune repertoires...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27853640/high-throughput-t-cell-receptor-sequencing-reveals-distinct-repertoires-between-tumor-and-adjacent-non-tumor-tissues-in-hbv-associated-hcc
#7
Yunqing Chen, Ying Xu, Miaoxian Zhao, Yu Liu, Mingxing Gong, Cantao Xie, Hongkai Wu, Zhanhui Wang
T lymphocytes, which recognize antigen peptides through specific T cell receptors (TCRs), play an important role in the human adaptive immune response. TCR diversity is closely associated with host immune response and cancer prognosis. Although tumor-infiltrating T lymphocytes have implications for tumor prognosis, few studies have performed a detailed characterization of TCR diversity in both tumor and non-tumor tissues in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Here, we performed high-throughput sequencing of the TCRβ chain complementarity determining region 3 (CDR3) of liver-infiltrating T cells from 48 HBV-associated HCC patients...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27849172/novel-e2-glycoprotein-tetramer-detects-hepatitis-c-virus-specific-memory-b-cells
#8
Maude Boisvert, Wanrui Zhang, Elizabeth J Elrod, Nicole F Bernard, Jean-Pierre Villeneuve, Julie Bruneau, Joseph Marcotrigiano, Naglaa H Shoukry, Arash Grakoui
Acute hepatitis C virus (HCV) infection culminates in viral persistence in the majority of cases. Abs that recognize the envelope glycoproteins E1 and E2 are generated during the late stages of acute infection, yet their contribution to spontaneous viral clearance remains controversial. Investigation of the humoral responses during acute HCV infection have been limited by the inability to directly identify and characterize HCV-specific B cells. In this study we describe the development of a novel tetramer of the E2 glycoprotein ectodomain (J6, genotype 2a strain), which allowed us to visualize E2-specific B cells longitudinally in the peripheral blood of HCV-infected individuals...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27849037/investigating-the-effect-of-as03-adjuvant-on-the-plasma-cell-repertoire-following-ph1n1-influenza-vaccination
#9
J D Galson, J Trück, D F Kelly, R van der Most
Influenza pandemics require rapid deployment of effective vaccines for control. Adjuvants such as AS03 improve vaccine immunogenicity, but this mechanism is poorly understood. We used high-throughput B cell receptor sequencing of plasma cells produced following AS03-adjuvanted and non-adjuvanted 2009 pandemic H1N1 vaccination, as well as pre-pandemic seasonal influenza vaccination to elucidate the effect of the adjuvant on the humoral immune response. By analyzing mutation levels, it was possible to distinguish sequences from cells that were recently activated from naïve B cells from those that were activated by memory recall...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27835690/vidjil-a-web-platform-for-analysis-of-high-throughput-repertoire-sequencing
#10
Marc Duez, Mathieu Giraud, Ryan Herbert, Tatiana Rocher, Mikaël Salson, Florian Thonier
BACKGROUND: The B and T lymphocytes are white blood cells playing a key role in the adaptive immunity. A part of their DNA, called the V(D)J recombinations, is specific to each lymphocyte, and enables recognition of specific antigenes. Today, with new sequencing techniques, one can get billions of DNA sequences from these regions. With dedicated Repertoire Sequencing (RepSeq) methods, it is now possible to picture population of lymphocytes, and to monitor more accurately the immune response as well as pathologies such as leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27830696/igd-attenuates-the-igm-induced-anergy-response-in-transitional-and-mature-b-cells
#11
Zahra Sabouri, Samuel Perotti, Emily Spierings, Peter Humburg, Mehmet Yabas, Hannes Bergmann, Keisuke Horikawa, Carla Roots, Samantha Lambe, Clara Young, T Dan Andrews, Matthew Field, Anselm Enders, Joanne H Reed, Christopher C Goodnow
Self-tolerance by clonal anergy of B cells is marked by an increase in IgD and decrease in IgM antigen receptor surface expression, yet the function of IgD on anergic cells is obscure. Here we define the RNA landscape of the in vivo anergy response, comprising 220 induced sequences including a core set of 97. Failure to co-express IgD with IgM decreases overall expression of receptors for self-antigen, but paradoxically increases the core anergy response, exemplified by increased Sdc1 encoding the cell surface marker syndecan-1...
November 10, 2016: Nature Communications
https://www.readbyqxmd.com/read/27829352/short-tandem-repeats-segmental-duplications-gene-deletion-and-genomic-instability-in-a-rapidly-diversified-immune-gene-family
#12
Matan Oren, Megan A Barela Hudgell, Brian D'Allura, Jacob Agronin, Alexandra Gross, Daniele Podini, L Courtney Smith
BACKGROUND: Genomic regions with repetitive sequences are considered unstable and prone to swift DNA diversification processes. A highly diverse immune gene family of the sea urchin (Strongylocentrotus purpuratus), called Sp185/333, is composed of clustered genes with similar sequence as well as several types of repeats ranging in size from short tandem repeats (STRs) to large segmental duplications. This repetitive structure may have been the basis for the incorrect assembly of this gene family in the sea urchin genome sequence...
November 9, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27825771/riches-in-rags-revealing-the-v-d-j-recombinase-through-high-resolution-structures
#13
REVIEW
Karla K Rodgers
Development of the adaptive immune system is dependent on V(D)J recombination, which forms functional antigen receptor genes through rearrangement of component gene segments. The V(D)J recombinase, comprising recombination-activating proteins RAG1 and RAG2, guides the initial DNA cleavage events to the recombination signal sequence (RSS), which flanks each gene segment. Although the enzymatic steps for RAG-mediated endonucleolytic activity were established over two decades ago, only recently have high-resolution structural studies of the catalytically active core regions of the RAG proteins shed light on conformational requirements for the reaction...
November 5, 2016: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/27825049/crystal-structure-of-a-polypeptide-s-c-terminus-in-complex-with-the-regulatory-domain-of-er-aminopeptidase-1
#14
Lufei Sui, Amit Gandhi, Hwai-Chen Guo
Endoplasmic reticulum aminopeptidase 1 (ERAP1) is involved in the final processing of peptide precursors to generate the N-termini of MHC class I-restricted epitopes. ERAP1 thus influences immunodominance and cytotoxic immune responses by controlling the peptide repertoire available for cell surface presentation by MHC molecules. To enable this critical role in antigen processing, ERAP1 trims peptides by a unique molecular ruler mechanism that turns on/off hydrolysis activity in a peptide-length and -sequence dependent manner...
November 5, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27820605/molecular-level-analysis-of-the-serum-antibody-repertoire-in-young-adults-before-and-after-seasonal-influenza-vaccination
#15
Jiwon Lee, Daniel R Boutz, Veronika Chromikova, M Gordon Joyce, Christopher Vollmers, Kwanyee Leung, Andrew P Horton, Brandon J DeKosky, Chang-Han Lee, Jason J Lavinder, Ellen M Murrin, Constantine Chrysostomou, Kam Hon Hoi, Yaroslav Tsybovsky, Paul V Thomas, Aliaksandr Druz, Baoshan Zhang, Yi Zhang, Lingshu Wang, Wing-Pui Kong, Daechan Park, Lyubov I Popova, Cornelia L Dekker, Mark M Davis, Chalise E Carter, Ted M Ross, Andrew D Ellington, Patrick C Wilson, Edward M Marcotte, John R Mascola, Gregory C Ippolito, Florian Krammer, Stephen R Quake, Peter D Kwong, George Georgiou
Molecular understanding of serological immunity to influenza has been confounded by the complexity of the polyclonal antibody response in humans. Here we used high-resolution proteomics analysis of immunoglobulin (referred to as Ig-seq) coupled with high-throughput sequencing of transcripts encoding B cell receptors (BCR-seq) to quantitatively determine the antibody repertoire at the individual clonotype level in the sera of young adults before and after vaccination with trivalent seasonal influenza vaccine...
November 7, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27818694/high-throughput-analysis-of-the-t-cell-receptor-beta-chain-repertoire-in-pbmcs-from-chronic-hepatitis-b-patients-with-hbeag-seroconversion
#16
Yachao Qu, Yong Huang, Di Liu, Yinuo Huang, Zhiyi Zhang, Zhiqiang Mi, Xiaoping An, Yigang Tong, Jun Lu
T lymphocytes are the most important immune cells that affect both the development and treatment of hepatitis B. We used high-throughput sequencing to determine the diversity in the V and J regions of the TCRβ chain in 4 chronic hepatitis B patients before and after HBeAg seroconversion. Here, we demonstrate that the 4 patients expressed Vβ12-4 at the highest frequencies of 10.6%, 9.2%, 17.5%, and 7.5%, and Vβ28 was the second most common, with frequencies of 7.8%, 6.7%, 5.3%, and 10.9%, respectively. No significant changes were observed following seroconversion...
2016: Canadian Journal of Infectious Diseases & Medical Microbiology
https://www.readbyqxmd.com/read/27815002/methodologic-considerations-in-the-application-of-next-generation-sequencing-of-human-trb-repertoires-for-clinical-use
#17
Liwen Xu, Xiaoqing You, PingPing Zheng, Bing M Zhang, Puja K Gupta, Philip Lavori, Everett Meyer, James L Zehnder
Next-generation sequencing (NGS) of immune receptors has become a standard tool to assess minimal residual disease (MRD) in patients treated for lymphoid malignancy, and it is being used to study the T-cell repertoire in many clinical settings. To better understanding the potential clinical utility and limitations of this application outside of MRD, we developed a BIOMED-2 primer-based NGS method and characterized its performance in controls and patients with graft-versus-host disease (GVHD) after allogeneic hematopoietic transplant...
November 1, 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27806695/insights-into-the-innate-immunome-of-actiniarians-using-a-comparative-genomic-approach
#18
Chloé A van der Burg, Peter J Prentis, Joachim M Surm, Ana Pavasovic
BACKGROUND: Innate immune genes tend to be highly conserved in metazoans, even in early divergent lineages such as Cnidaria (jellyfish, corals, hydroids and sea anemones) and Porifera (sponges). However, constant and diverse selection pressures on the immune system have driven the expansion and diversification of different immune gene families in a lineage-specific manner. To investigate how the innate immune system has evolved in a subset of sea anemone species (Order: Actiniaria), we performed a comprehensive and comparative study using 10 newly sequenced transcriptomes, as well as three publically available transcriptomes, to identify the origins, expansions and contractions of candidate and novel immune gene families...
November 2, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27799928/evaluation-of-the-antigen-experienced-b-cell-receptor-repertoire-in-healthy-children-and-adults
#19
Hanna IJspeert, Pauline A van Schouwenburg, David van Zessen, Ingrid Pico-Knijnenburg, Gertjan J Driessen, Andrew P Stubbs, Mirjam van der Burg
Upon antigen recognition via their B cell receptor (BR), B cells migrate to the germinal center where they undergo somatic hypermutation (SHM) to increase their affinity for the antigen, and class switch recombination (CSR) to change the effector function of the secreted antibodies. These steps are essential to create an antigen-experienced BR repertoire that efficiently protects the body against pathogens. At the same time, the BR repertoire should be selected to protect against responses to self-antigen or harmless antigens...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27796362/reconstituted-b-cell-receptor-signaling-reveals-carbohydrate-dependent-mode-of-activation
#20
Rina F Villar, Jinal Patel, Grant C Weaver, Masaru Kanekiyo, Adam K Wheatley, Hadi M Yassine, Catherine E Costello, Kevin B Chandler, Patrick M McTamney, Gary J Nabel, Adrian B McDermott, John R Mascola, Steven A Carr, Daniel Lingwood
Activation of immune cells (but not B cells) with lectins is widely known. We used the structurally defined interaction between influenza hemagglutinin (HA) and its cell surface receptor sialic acid (SA) to identify a B cell receptor (BCR) activation modality that proceeded through non-cognate interactions with antigen. Using a new approach to reconstitute antigen-receptor interactions in a human reporter B cell line, we found that sequence-defined BCRs from the human germline repertoire could be triggered by both complementarity to influenza HA and a separate mode of signaling that relied on multivalent ligation of BCR sialyl-oligosaccharide...
October 31, 2016: Scientific Reports
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