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Immune repertoire sequencing

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https://www.readbyqxmd.com/read/28332079/gorilla-mhc-class-i-gene-and-sequence-variation-in-a-comparative-context
#1
Jörg B Hans, Richard A Bergl, Linda Vigilant
Comparisons of MHC gene content and diversity among closely related species can provide insights into the evolutionary mechanisms shaping immune system variation. After chimpanzees and bonobos, gorillas are humans' closest living relatives; but in contrast, relatively little is known about the structure and variation of gorilla MHC class I genes (Gogo). Here, we combined long-range amplifications and long-read sequencing technology to analyze full-length MHC class I genes in 35 gorillas. We obtained 50 full-length genomic sequences corresponding to 15 Gogo-A alleles, 4 Gogo-Oko alleles, 21 Gogo-B alleles, and 10 Gogo-C alleles including 19 novel coding region sequences...
March 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28323873/a-three-monoclonal-antibody-combination-potently-neutralizes-multiple-botulinum-neurotoxin-serotype-f-subtypes
#2
Yongfeng Fan, Consuelo Garcia-Rodriguez, Jianlong Lou, Weihua Wen, Fraser Conrad, Wenwu Zhai, Theresa J Smith, Leonard A Smith, James D Marks
Human botulism is primarily caused by botulinum neurotoxin (BoNT) serotypes A, B and E, with around 1% caused by serotype F (BoNT/F). BoNT/F comprises at least seven different subtypes with the amino acid sequence difference between subtypes as high as 36%. The sequence differences present a significant challenge for generating monoclonal antibodies (mAbs) that can bind, detect and neutralize all BoNT/F subtypes. We used repertoire cloning of immune mouse antibody variable (V) regions and yeast display to generate a panel of 33 lead single chain Fv (scFv) mAbs that bound one or more BoNT/F subtypes with a median equilibrium dissociation constant (KD) of 4...
2017: PloS One
https://www.readbyqxmd.com/read/28321219/computational-model-reveals-limited-correlation-between-germinal-center-b-cell-subclone-abundancy-and-affinity-implications-for-repertoire-sequencing
#3
Polina Reshetova, Barbera D C van Schaik, Paul L Klarenbeek, Marieke E Doorenspleet, Rebecca E E Esveldt, Paul-Peter Tak, Jeroen E J Guikema, Niek de Vries, Antoine H C van Kampen
Immunoglobulin repertoire sequencing has successfully been applied to identify expanded antigen-activated B-cell clones that play a role in the pathogenesis of immune disorders. One challenge is the selection of the Ag-specific B cells from the measured repertoire for downstream analyses. A general feature of an immune response is the expansion of specific clones resulting in a set of subclones with common ancestry varying in abundance and in the number of acquired somatic mutations. The expanded subclones are expected to have BCR affinities for the Ag higher than the affinities of the naive B cells in the background population...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28318808/t-cell-receptor-assessment-in-autoimmune-disease-requires-access-to-the-most-adjacent-immunologically-active-organ
#4
Bergithe E Oftedal, Brita Ardesjö Lundgren, David Hamm, Poh-Yi Gan, Stephen R Holdsworth, Christopher N Hahn, Andreas W Schreiber, Hamish S Scott
Next generation sequencing of T and B cell receptors is emerging as a valuable and effective method to diagnose and monitor hematopoietic malignancies. So far, this approach has not been fully explored in regard to autoimmune diseases. T cells develop in the thymus where they undergo positive and negative selection, and the autoimmune regulator (Aire) is central in the establishment of immunological tolerance. Loss of Aire leads to severe multiorgan autoimmune disease with infiltration of autoreactive T cells in affected organs...
March 15, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28284194/clonocalc-and-clonoplot-immune-repertoire-analysis-from-raw-files-to-publication-figures-with-graphical-user-interface
#5
Anke Fähnrich, Moritz Krebbel, Normann Decker, Martin Leucker, Felix D Lange, Kathrin Kalies, Steffen Möller
BACKGROUND: Next generation sequencing (NGS) technologies enable studies and analyses of the diversity of both T and B cell receptors (TCR and BCR) in human and animal systems to elucidate immune functions in health and disease. Over the last few years, several algorithms and tools have been developed to support respective analyses of raw sequencing data of the immune repertoire. These tools focus on distinct aspects of the data processing and require a strong bioinformatics background...
March 11, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28281773/b-cell-epitopes-of-african-horse-sickness-virus-serotype-4-recognised-by-immune-horse-sera
#6
Evans M Mathebula, Frederika E Faber, Wouter Van Wyngaardt, Antoinette Van Schalkwyk, Alri Pretorius, Jeanni Fehrsen
Identifying antigenic proteins and mapping their epitopes is important for the development of diagnostic reagents and recombinant vaccines. B-cell epitopes of African horse sickness virus (AHSV) have previously been mapped on VP2, VP5, VP7 and NS1, using mouse, rabbit and chicken monoclonal antibodies. A comprehensive study of the humoral immune response of five vaccinated horses to AHSV-4 antigenic peptides was undertaken. A fragmented-genome phage display library expressing a repertoire of AHSV-4 peptides spanning the entire genome was constructed...
February 24, 2017: Onderstepoort Journal of Veterinary Research
https://www.readbyqxmd.com/read/28264647/the-repertoire-dissimilarity-index-as-a-method-to-compare-lymphocyte-receptor-repertoires
#7
Christopher R Bolen, Florian Rubelt, Jason A Vander Heiden, Mark M Davis
BACKGROUND: The B and T cells of the human adaptive immune system leverage a highly diverse repertoire of antigen-specific receptors to protect the human body from pathogens. The sequencing and analysis of immune repertoires is emerging as an important tool to understand immune responses, whether beneficial or harmful (in the case of autoimmunity). However, methods for studying these repertoires, and for directly comparing different immune repertoires, are lacking. RESULTS: In this paper, we present a non-parametric method for directly comparing sequencing repertoires, with the goal of rigorously quantifying differences in V, D, and J gene segment utilization...
March 7, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28259700/describing-the-diversity-of-ag-specific-receptors-in-vertebrates-contribution-of-repertoire-deep-sequencing
#8
Rosario Castro, Sofie Navelsaker, Aleksei Krasnov, Louis Du Pasquier, Pierre Boudinot
During the last decades, gene and cDNA cloning identified TCR and Ig genes across vertebrates; genome sequencing of TCR and Ig loci in many species revealed the different organizations selected during evolution under the pressure of generating diverse repertoires of Ag receptors. By detecting clonotypes over a wide range of frequency, deep sequencing of Ig and TCR transcripts provides a new way to compare the structure of expressed repertoires in species of various sizes, at different stages of development, with different physiologies, and displaying multiple adaptations to the environment...
March 1, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28254787/serine-proteases-enhance-immunogenic-antigen-presentation-on-lung-cancer-cells
#9
Haley L Peters, Satyendra C Tripathi, Celine Kerros, Hiroyuki Katayama, Haven R Garber, Lisa S St John, Lorenzo Federico, Ismail M Meraz, Jack A Roth, Boris Sepesi, Mourad Majidi, Kathryn Ruisaard, Karen Clise-Dwyer, Jason Roszik, Don L Gibbons, John Heymach, Stephen G Swisher, Chantale Bernantchez, Gheath Alatrash, Samir M Hanash, Jeffrey J Molldrem
Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these re-invigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3...
March 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28251903/integrated-molecular-analysis-of-tumor-biopsies-on-sequential-ctla-4-and-pd-1-blockade-reveals-markers-of-response-and-resistance
#10
Whijae Roh, Pei-Ling Chen, Alexandre Reuben, Christine N Spencer, Peter A Prieto, John P Miller, Vancheswaran Gopalakrishnan, Feng Wang, Zachary A Cooper, Sangeetha M Reddy, Curtis Gumbs, Latasha Little, Qing Chang, Wei-Shen Chen, Khalida Wani, Mariana Petaccia De Macedo, Eveline Chen, Jacob L Austin-Breneman, Hong Jiang, Jason Roszik, Michael T Tetzlaff, Michael A Davies, Jeffrey E Gershenwald, Hussein Tawbi, Alexander J Lazar, Patrick Hwu, Wen-Jen Hwu, Adi Diab, Isabella C Glitza, Sapna P Patel, Scott E Woodman, Rodabe N Amaria, Victor G Prieto, Jianhua Hu, Padmanee Sharma, James P Allison, Lynda Chin, Jianhua Zhang, Jennifer A Wargo, P Andrew Futreal
Immune checkpoint blockade produces clinical benefit in many patients. However, better biomarkers of response are still needed, and mechanisms of resistance remain incompletely understood. To address this, we recently studied a cohort of melanoma patients treated with sequential checkpoint blockade against cytotoxic T lymphocyte antigen-4 (CTLA-4) followed by programmed death receptor-1 (PD-1) and identified immune markers of response and resistance. Building on these studies, we performed deep molecular profiling including T cell receptor sequencing and whole-exome sequencing within the same cohort and demonstrated that a more clonal T cell repertoire was predictive of response to PD-1 but not CTLA-4 blockade...
March 1, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28248310/clonal-selection-in-the-human-v%C3%AE-1-t-cell-repertoire-indicates-%C3%AE-%C3%AE-tcr-dependent-adaptive-immune-surveillance
#11
Martin S Davey, Carrie R Willcox, Stephen P Joyce, Kristin Ladell, Sofya A Kasatskaya, James E McLaren, Stuart Hunter, Mahboob Salim, Fiyaz Mohammed, David A Price, Dmitriy M Chudakov, Benjamin E Willcox
γδ T cells are considered to be innate-like lymphocytes that respond rapidly to stress without clonal selection and differentiation. Here we use next-generation sequencing to probe how this paradigm relates to human Vδ2(neg) T cells, implicated in responses to viral infection and cancer. The prevalent Vδ1 T cell receptor (TCR) repertoire is private and initially unfocused in cord blood, typically becoming strongly focused on a few high-frequency clonotypes by adulthood. Clonal expansions have differentiated from a naive to effector phenotype associated with CD27 downregulation, retaining proliferative capacity and TCR sensitivity, displaying increased cytotoxic markers and altered homing capabilities, and remaining relatively stable over time...
March 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28246356/differential-antibody-responses-to-conserved-hiv-1-neutralizing-epitopes-in-the-context-of-multivalent-scaffolds-and-native-like-gp140-trimers
#12
Charles D Morris, Parisa Azadnia, Natalia de Val, Nemil Vora, Andrew Honda, Erick Giang, Karen Saye-Francisco, Yushao Cheng, Xiaohe Lin, Colin J Mann, Jeffrey Tang, Devin Sok, Dennis R Burton, Mansun Law, Andrew B Ward, Linling He, Jiang Zhu
Broadly neutralizing antibodies (bNAbs) have provided valuable insights into the humoral immune response to HIV-1. While rationally designed epitope scaffolds and well-folded gp140 trimers have been proposed as vaccine antigens, a comparative understanding of their antibody responses has not yet been established. In this study, we probed antibody responses to the N332 supersite and the membrane-proximal external region (MPER) in the context of heterologous protein scaffolds and native-like gp140 trimers. Ferritin nanoparticles and fragment crystallizable (Fc) regions were utilized as multivalent carriers to display scaffold antigens with grafted N332 and MPER epitopes, respectively...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28241742/3d-diversity-dynamics-differential-testing-a-proposed-pipeline-for-analysis-of-next-generation-sequencing-t-cell-repertoire-data
#13
Li Zhang, Jason Cham, Alan Paciorek, James Trager, Nadeem Sheikh, Lawrence Fong
BACKGROUND: Cancer immunotherapy has demonstrated significant clinical activity in different cancers. T cells represent a crucial component of the adaptive immune system and are thought to mediate anti-tumoral immunity. Antigen-specific recognition by T cells is via the T cell receptor (TCR) which is unique for each T cell. Next generation sequencing (NGS) of the TCRs can be used as a platform to profile the T cell repertoire. Though there are a number of software tools available for processing repertoire data by mapping antigen receptor segments to sequencing reads and assembling the clonotypes, most of them are not designed to track and examine the dynamic nature of the TCR repertoire across multiple time points or between different biologic compartments (e...
February 27, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28230642/strategies-to-obtain-diverse-and-specific-human-monoclonal-antibodies-from-transgenic-animals
#14
Marianne Brüggemann, Michael J Osborn, Biao Ma, Roland Buelow
Techniques to obtain large quantities of antigen-specific monoclonal antibodies, mAbs, were first established in the 1970s when Georges Köhler and César Milstein immortalized antibody-producing mouse B-lymphocytes by fusion with myeloma cells (http://www.whatisbiotechnology.org/exhibitions/milstein). Combined with the expression of human antibodies in transgenic animals, this technique allowed upon immunization the generation of highly specific fully human mAbs for therapeutic applications. Apart from being extremely beneficial, mAbs are a huge success commercially...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28218745/human-%C3%AE-%C3%AE-t-cells-are-quickly-reconstituted-after-stem-cell-transplantation-and-show-adaptive-clonal-expansion-in-response-to-viral-infection
#15
Sarina Ravens, Christian Schultze-Florey, Solaiman Raha, Inga Sandrock, Melanie Drenker, Linda Oberdörfer, Annika Reinhardt, Inga Ravens, Maleen Beck, Robert Geffers, Constantin von Kaisenberg, Michael Heuser, Felicitas Thol, Arnold Ganser, Reinhold Förster, Christian Koenecke, Immo Prinz
To investigate how the human γδ T cell pool is shaped during ontogeny and how it is regenerated after transplantation of hematopoietic stem cells (HSCs), we applied an RNA-based next-generation sequencing approach to monitor the dynamics of the repertoires of γδ T cell antigen receptors (TCRs) before and after transplantation in a prospective cohort study. We found that repertoires of rearranged genes encoding γδ TCRs (TRG and TRD) in the peripheral blood of healthy adults were stable over time. Although a large fraction of human TRG repertoires consisted of public sequences, the TRD repertoires were private...
February 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28217133/a-perspective-on-crn-proteins-in-the-genomics-age-evolution-classification-delivery-and-function-revisited
#16
REVIEW
Tiago M M M Amaro, Gaëtan J A Thilliez, Graham B Motion, Edgar Huitema
Plant associated microbes rely on secreted virulence factors (effectors) to modulate host immunity and ensure progressive infection. Amongst the secreted protein repertoires defined and studied in pathogens to date, the CRNs (for CRinkling and Necrosis) have emerged as one of only a few highly conserved protein families, spread across several kingdoms. CRN proteins were first identified in plant pathogenic oomycetes where they were found to be modular factors that are secreted and translocated inside host cells by means of a conserved N-terminal domain...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28213050/reduced-frequency-of-two-activating-kir-genes-in-patients-with-sepsis
#17
Luciana M Oliveira, Pamela Portela, Joice Merzoni, Juliana D Lindenau, Fernando S Dias, Jaqueline Beppler, Pietra Graebin, Clarice S Alho, Gilberto Schwartsmann, Felipe Dal-Pizzol, Luiz Fernando Jobim, Mariana Jobim, Rafael Roesler
Natural killer (NK) cell activity is regulated by activating and inhibitory signals transduced by killer cell immunoglobulin-like receptors (KIR). Diversity in KIR gene repertoire among individuals may affect disease outcome. Sepsis development and severity may be influenced by genetic factors affecting the immune response. Here, we examined sixteen KIR genes and their human leucocyte antigen (HLA) class I ligands in critical patients, aiming to identify patterns that could be associated with sepsis. Male and female patients (ages ranging between 14 and 94years-old) were included...
February 14, 2017: Human Immunology
https://www.readbyqxmd.com/read/28201988/molecular-characterization-of-mhc-class-iib-genes-of-sympatric-neotropical-cichlids
#18
Melinda J Hofmann, Seraina E Bracamonte, Christophe Eizaguirre, Marta Barluenga
BACKGROUND: The Major Histocompatibility Complex (MHC) is a key component of the adaptive immune system of all vertebrates and consists of the most polymorphic genes known to date. Due to this complexity, however, MHC remains to be characterized in many species including any Neotropical cichlid fish. Neotropical crater lake cichlids are ideal models to study evolutionary processes as they display one of the most convincing examples of sympatric and repeated parallel radiation events within and among isolated crater lakes...
February 15, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28196891/insights-into-immune-system-development-and-function-from-mouse-t-cell-repertoires
#19
Zachary Sethna, Yuval Elhanati, Chrissy S Dudgeon, Curtis G Callan, Arnold J Levine, Thierry Mora, Aleksandra M Walczak
The ability of the adaptive immune system to respond to arbitrary pathogens stems from the broad diversity of immune cell surface receptors. This diversity originates in a stochastic DNA editing process (VDJ recombination) that acts on the surface receptor gene each time a new immune cell is created from a stem cell. By analyzing T-cell receptor (TCR) sequence repertoires taken from the blood and thymus of mice of different ages, we quantify the changes in the VDJ recombination process that occur from embryo to young adult...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193177/anopheline-salivary-protein-genes-and-gene-families-an-evolutionary-overview-after-the-whole-genome-sequence-of-sixteen-anopheles-species
#20
Bruno Arcà, Fabrizio Lombardo, Claudio J Struchiner, José M C Ribeiro
BACKGROUND: Mosquito saliva is a complex cocktail whose pharmacological properties play an essential role in blood feeding by counteracting host physiological response to tissue injury. Moreover, vector borne pathogens are transmitted to vertebrates and exposed to their immune system in the context of mosquito saliva which, in virtue of its immunomodulatory properties, can modify the local environment at the feeding site and eventually affect pathogen transmission. In addition, the host antibody response to salivary proteins may be used to assess human exposure to mosquito vectors...
February 13, 2017: BMC Genomics
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