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Repertoire Bioinformatics Immune

Ronit Rosenfeld, Anat Zvi, Eitan Winter, Ronen Hope, Ofir Israeli, Ohad Mazor, Gur Yaari
Recombinant antibodies serve as therapeutic molecules for a broad range of applications. High affinity antibodies are typically isolated following an active and effective immunization. Human-like antibodies may be obtained from immunized nonhuman primates (NHP), such as rhesus macaque, when immunized human origin is not available. For the isolation of such antibodies, strategies like phage and yeast display, are employed. These strategies are primarily based on the amplification of the rearranged variable (V) regions coded by mRNA, obtained from lymphatic source of immunized animals...
November 22, 2018: Journal of Immunological Methods
M Pinto, A González-Díaz, M P Machado, S Duarte, L Vieira, J A Carriço, S Marti, M P Bajanca-Lavado, J P Gomes
The human-restricted bacterium Haemophilus influenzae is responsible for respiratory infections in both children and adults. While colonization begins in the upper airways, it can spread throughout the respiratory tract potentially leading to invasive infections. Although the spread of H. influenzae serotype b (Hib) has been prevented by vaccination, the emergence of infections by other serotypes as well as by non-typeable isolates (NTHi) have been observed, prompting the need for novel prevention strategies...
October 31, 2018: Infection, Genetics and Evolution
Melissah Rowe, Sheri Skerget, Matthew A Rosenow, Timothy L Karr
Spermatozoa exhibit remarkable variability in size, shape, and performance. Our understanding of the molecular basis of this variation, however, is limited, especially in avian taxa. The zebra finch (Taeniopygia guttata) is a model organism in the study of avian sperm biology and sperm competition. Using LC-MS based proteomics, we identify and describe 494 proteins of the zebra finch sperm proteome (ZfSP). Gene ontology and associated bioinformatics analyses revealed a rich repertoire of proteins essential to sperm structure and function, including proteins linked to metabolism and energetics, as well as tubulin binding and microtubule related functions...
October 23, 2018: Journal of Proteomics
Alexander Dimitri Yermanos, Andreas Kevin Dounas, Tanja Stadler, Annette Oxenius, Sai T Reddy
Antibody evolution studies have been traditionally limited to either tracing a single clonal lineage (B cells derived from a single V-(D)-J recombination) over time or examining bulk functionality changes (e.g., tracing serum polyclonal antibody proteins). Studying a single B cell disregards the majority of the humoral immune response, whereas bulk functional studies lack the necessary resolution to analyze the co-existing clonal diversity. Recent advances in high-throughput sequencing (HTS) technologies and bioinformatics have made it possible to examine multiple co-evolving antibody monoclonal lineages within the context of a single repertoire...
2018: Frontiers in Immunology
Pouya Faridi, Chen Li, Sri H Ramarathinam, Julian P Vivian, Patricia T Illing, Nicole A Mifsud, Rochelle Ayala, Jiangning Song, Linden J Gearing, Paul J Hertzog, Nicola Ternette, Jamie Rossjohn, Nathan P Croft, Anthony W Purcell
The diversity of peptides displayed by class I human leukocyte antigen (HLA) plays an essential role in T cell immunity. The peptide repertoire is extended by various posttranslational modifications, including proteasomal splicing of peptide fragments from distinct regions of an antigen to form nongenomically templated cis-spliced sequences. Previously, it has been suggested that a fraction of the immunopeptidome constitutes such cis-spliced peptides; however, because of computational limitations, it has not been possible to assess whether trans-spliced peptides (i...
October 12, 2018: Science Immunology
Valerie Odon, Iliana Georgana, Joe Holley, Jordi Morata, Carlos Maluquer de Motes
Ankyrin repeat (ANK) domains are one of the most abundant motifs in eukaryotic proteins. ANK proteins are rare amongst viruses with the exception of poxviruses, which presumably acquired them from the host via horizontal gene transfer. The architecture of poxvirus ANK proteins is however different from their cellular counterparts and this precludes a direct acquisition event. Here we combine bioinformatics analysis and quantitative proteomics to discovera new class of viral ANK proteins with a domain organisation that relates to cellular ANK proteins...
September 26, 2018: Journal of Virology
Patrick V Holec, Joseph Berleant, Mark Bathe, Michael E Birnbaum
Motivation: The study of T cell receptor repertoires has generated new insights into immune system recognition. However, the ability to robustly characterize these populations has been limited by technical barriers and an inability to reliably infer heterodimeric chain pairings for T cell receptors. Results: Here, we describe a novel analytical approach to an emerging immune repertoire sequencing method, improving the resolving power of this low-cost technology...
September 12, 2018: Bioinformatics
Kerry A Ramsbottom, Daniel F Carr, Andrew R Jones, Daniel J Rigden
Adverse drug reactions have been linked with genetic polymorphisms in HLA genes in numerous different studies. HLA proteins have an essential role in the presentation of self and non-self peptides, as part of the adaptive immune response. Amongst the associated drugs-allele combinations, anti-HIV drug Abacavir has been shown to be associated with the HLA-B*57:01 allele, and anti-epilepsy drug Carbamazepine with B*15:02, in both cases likely following the altered peptide repertoire model of interaction. Under this model, the drug binds directly to the antigen presentation region, causing different self peptides to be presented, which trigger an unwanted immune response...
September 2018: Molecular Immunology
Magdalena Migalska, Alvaro Sebastian, Jacek Radwan
In recent years, immune repertoire profiling with high-throughput sequencing (HTS) has advanced our understanding of adaptive immunity. However, fast progress in the field applied mostly to human and mouse research, with only few studies devoted to other model vertebrates. We present the first in-depth characterization of the T-cell receptor (TCR) repertoire in a non-model mammal (bank vole, Myodes glareolus), widely used in ecological and evolutionary research. We used RNA from spleens, 5'RACE and HTS to describe V and J segments of TCRβ, qualitatively characterize preferential V-J segment usage and CDR3 length distribution...
August 2, 2018: Scientific Reports
Emanuele Sasso, Chiara D'Avino, Margherita Passariello, Anna Morena D'Alise, Daniela Siciliano, Maria Luisa Esposito, Guendalina Froechlich, Riccardo Cortese, Elisa Scarselli, Nicola Zambrano, Alfredo Nicosia, Claudia De Lorenzo
Immune checkpoints are emerging as novel targets for cancer therapy, and antibodies against them have shown remarkable clinical efficacy with potential for combination treatments to achieve high therapeutic index. This work aims at providing a novel approach for the generation of several novel human immunomodulatory antibodies capable of binding their targets in their native conformation and useful for therapeutic applications. We performed a massive parallel screening of phage libraries by using for the first time activated human lymphocytes to generate large collections of single-chain variable fragments (scFvs) against 10 different immune checkpoints: LAG-3, PD-L1, PD-1, TIM3, BTLA, TIGIT, OX40, 4-1BB, CD27 and ICOS...
October 2018: MAbs
Serra E Elliott, Sarah Kongpachith, Nithya Lingampalli, Julia Z Adamska, Bryan J Cannon, Rong Mao, Lisa K Blum, William H Robinson
OBJECTIVE: Rheumatoid arthritis (RA) is characterized by the presence of anti-citrullinated protein antibodies (ACPAs); nevertheless, the origin, specificity, and functional properties of ACPAs remain poorly understood. The aim of this study was to characterize the evolution of ACPAs by sequencing the plasmablast antibody repertoire at serial time points in patients with established RA. METHODS: Blood samples were obtained at up to 4 serial time points from 8 individuals with established RA who were positive for ACPAs by the anti-cyclic citrullinated peptide test...
December 2018: Arthritis & Rheumatology
Ludmila Danilova, Valsamo Anagnostou, Justina X Caushi, John-William Sidhom, Haidan Guo, Hok Yee Chan, Prerna Suri, Ada 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 M Pardoll, Franck Housseau, Kellie N Smith
Mutation-associated neoantigens (MANA) 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 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 T-cell receptor sequencing of short-term, peptide-stimulated cultures with a bioinformatic platform to identify antigen-specific clonotypic amplifications...
August 2018: Cancer Immunology Research
Scott Christley, Walter Scarborough, Eddie Salinas, William H Rounds, Inimary T Toby, John M Fonner, Mikhail K Levin, Min Kim, Stephen A Mock, Christopher Jordan, Jared Ostmeyer, Adam Buntzman, Florian Rubelt, Marco L Davila, Nancy L Monson, Richard H Scheuermann, Lindsay G Cowell
Background: Recent technological advances in immune repertoire sequencing have created tremendous potential for advancing our understanding of adaptive immune response dynamics in various states of health and disease. Immune repertoire sequencing produces large, highly complex data sets, however, which require specialized methods and software tools for their effective analysis and interpretation. Results: VDJServer is a cloud-based analysis portal for immune repertoire sequence data that provide access to a suite of tools for a complete analysis workflow, including modules for preprocessing and quality control of sequence reads, V(D)J gene segment assignment, repertoire characterization, and repertoire comparison...
2018: Frontiers in Immunology
Stacey L Wooden, Wayne C Koff
Although the success of vaccination to date has been unprecedented, our inadequate understanding of the details of the human immune response to immunization has resulted in several recent vaccine failures and significant delays in the development of high-need vaccines for global infectious diseases and cancer. Because of the need to better understand the immense complexity of the human immune system, the Human Vaccines Project was launched in 2015 with the mission to decode the human immune response to accelerate development of vaccines and immunotherapies for major diseases...
2018: Human Vaccines & Immunotherapeutics
Christos Maramis, Athanasios Gkoufas, Anna Vardi, Evangelia Stalika, Kostas Stamatopoulos, Anastasia Hatzidimitriou, Nicos Maglaveras, Ioanna Chouvarda
BACKGROUND: The study of the huge diversity of immune receptors, often referred to as immune repertoire profiling, is a prerequisite for diagnosis, prognostication and monitoring of hematological disorders. In the era of high-throughput sequencing (HTS), the abundance of immunogenetic data has revealed unprecedented opportunities for the thorough profiling of T-cell receptors (TR) and B-cell receptors (BcR). However, the volume of the data to be analyzed mandates for efficient and ease-to-use immune repertoire profiling software applications...
April 18, 2018: BMC Bioinformatics
Tatsuo Ichinohe, Takahiko Miyama, Takakazu Kawase, Yasuko Honjo, Kazutaka Kitaura, Hiroyuki Sato, Tadasu Shin-I, Ryuji Suzuki
The human immune system is a fine network consisted of the innumerable numbers of functional cells that balance the immunity and tolerance against various endogenous and environmental challenges. Although advances in modern immunology have revealed a role of many unique immune cell subsets, technologies that enable us to capture the whole landscape of immune responses against specific antigens have been not available to date. Acquired immunity against various microorganisms including host microbiome is principally founded on T cell and B cell populations, each of which expresses antigen-specific receptors that define a unique clonotype...
2018: Frontiers in Immunology
Simone Rizzetto, David N P Koppstein, Jerome Samir, Mandeep Singh, Joanne H Reed, Curtis H Cai, Andrew R Lloyd, Auda A Eltahla, Christopher C Goodnow, Fabio Luciani
Motivation: The B-cell receptor (BCR) performs essential functions for the adaptive immune system including recognition of pathogen-derived antigens. The vast repertoire and adaptive variation of BCR sequences due to V(D)J recombination and somatic hypermutation necessitates single-cell characterization of BCR sequences. Single-cell RNA sequencing presents the opportunity for simultaneous capture of paired BCR heavy and light chains and the transcriptomic signature. Results: We developed VDJPuzzle, a novel bioinformatic tool that reconstructs productive, full-length B-cell receptor sequences of both heavy and light chains and extract somatic mutations on the VDJ region...
August 15, 2018: Bioinformatics
Nathalie Vigneron, Vincent Stroobant, Violette Ferrari, Joanna Abi Habib, Benoit J Van den Eynde
CD8+ cytolytic T lymphocytes are essential players of anti-tumor immune responses. On tumors, they recognize peptides of about 8-to-10 amino acids that generally result from the degradation of cellular proteins by the proteasome. Until a decade ago, these peptides were thought to solely correspond to linear fragments of proteins that were liberated after the hydrolysis of the peptide bonds located at their extremities. However, several examples of peptides containing two fragments originally distant in the protein sequence challenged this concept and demonstrated that proteasome could also splice peptides together by creating a new peptide bond between two distant fragments...
April 9, 2018: Molecular Immunology
Minglin Ou, Fengping Zheng, Xinzhou Zhang, Song Liu, Donge Tang, Peng Zhu, Jingjun Qiu, Yong Dai
Immunoglobulin A nephropathy (IgAN) is a type of glomerular disorder associated with immune dysregulation, and understanding B‑/T‑cell receptors (BCRs/TCRs) may be valuable for the development of specific immunotherapeutic interventions. In the present study, B and T cells were isolated from IgAN patients and healthy controls, and the composition of the BCR/TCR complementarity‑determining region (CDR)3 was analyzed by multiplex polymerase chain reaction, high‑throughput sequencing and bioinformatics...
May 2018: Molecular Medicine Reports
Daria Augustyniak, Rafał Seredyński, Siobhán McClean, Justyna Roszkowiak, Bartosz Roszniowski, Darren L Smith, Zuzanna Drulis-Kawa, Paweł Mackiewicz
Moraxella catarrhalis is a common human respiratory tract pathogen. Its virulence factors associated with whole bacteria or outer membrane vesicles (OMVs) aid infection, colonization and may induce specific antibodies. To investigate pathogen-host interactions, we applied integrated bioinformatic and immunoproteomic (2D-electrophoresis, immunoblotting, LC-MS/MS) approaches. We showed that OMV proteins engaged exclusively in complement evasion and colonization strategies, but not those involved in iron transport and metabolism, are major targets for cross-reacting antibodies produced against phylogenetically divergent M...
March 21, 2018: Scientific Reports
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