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Immune repertoire sequencing

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https://www.readbyqxmd.com/read/29776088/how-nonuniform-contact-profiles-of-t-cell-receptors-modulate-thymic-selection-outcomes
#1
Hanrong Chen, Arup K Chakraborty, Mehran Kardar
T cell receptors (TCRs) bind foreign or self-peptides attached to major histocompatibility complex (MHC) molecules, and the strength of this interaction determines T cell activation. Optimizing the ability of T cells to recognize a diversity of foreign peptides yet be tolerant of self-peptides is crucial for the adaptive immune system to properly function. This is achieved by selection of T cells in the thymus, where immature T cells expressing unique, stochastically generated TCRs interact with a large number of self-peptide-MHC; if a TCR does not bind strongly enough to any self-peptide-MHC, or too strongly with at least one self-peptide-MHC, the T cell dies...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29774030/changes-in-the-tcr%C3%AE-repertoire-and-tumor-immune-signature-from-a-cutaneous-melanoma-patient-immunized-with-the-csf-470-vaccine-a-case-report
#2
Mariana Aris, Alicia Inés Bravo, María Betina Pampena, Paula Alejandra Blanco, Ibel Carri, Daniel Koile, Patricio Yankilevich, Estrella Mariel Levy, María Marcela Barrio, José Mordoh
The allogeneic therapeutic vaccine CSF-470 has demonstrated a significant benefit over medium-dose IFNα2b in the distant metastasis-free survival for stages IIB-IIC-III cutaneous melanoma patients in a randomized phase II/III clinical trial (CASVAC-0401, NCT01729663). At the end of the 2-year CSF-470 immunization protocol, patient #006 developed several lung and one subcutaneous melanoma metastases; this later was excised. In this report, we analyzed the changes throughout vaccination of immune populations in blood and in the tumor tissue, with special focus on the T-cell repertoire...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29774024/quantification-of-hla-dm-dependent-major-histocompatibility-complex-of-class-ii-immunopeptidomes-by-the-peptide-landscape-antigenic-epitope-alignment-utility
#3
Miguel Álvaro-Benito, Eliot Morrison, Esam T Abualrous, Benno Kuropka, Christian Freund
The major histocompatibility complex of class II (MHCII) immunopeptidome represents the repertoire of antigenic peptides with the potential to activate CD4+ T cells. An understanding of how the relative abundance of specific antigenic epitopes affects the outcome of T cell responses is an important aspect of adaptive immunity and offers a venue to more rationally tailor T cell activation in the context of disease. Recent advances in mass spectrometric instrumentation, computational power, labeling strategies, and software analysis have enabled an increasing number of stratified studies on HLA ligandomes, in the context of both basic and translational research...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29763438/phasome-analysis-of-pathogenic-and-commensal-neisseria-species-expands-the-known-repertoire-of-phase-variable-genes-and-highlights-common-adaptive-strategies
#4
Joseph J Wanford, Luke R Green, Jack Aidley, Christopher D Bayliss
Pathogenic Neisseria are responsible for significantly higher levels of morbidity and mortality than their commensal relatives despite having similar genetic contents. Neisseria possess a disparate arsenal of surface determinants that facilitate host colonisation and evasion of the immune response during persistent carriage. Adaptation to rapid changes in these hostile host environments is enabled by phase variation (PV) involving high frequency, stochastic switches in expression of surface determinants. In this study, we analysed 89 complete and 79 partial genomes, from the NCBI and Neisseria PubMLST databases, representative of multiple pathogenic and commensal species of Neisseria using PhasomeIt, a new program that identifies putatively phase-variable genes and homology groups by the presence of simple sequence repeats (SSR)...
2018: PloS One
https://www.readbyqxmd.com/read/29755475/impact-of-a-3-months-vegetarian-diet-on-the-gut-microbiota-and-immune-repertoire
#5
Chenchen Zhang, Andrea Björkman, Kaiye Cai, Guilin Liu, Chunlin Wang, Yin Li, Huihua Xia, Lijun Sun, Karsten Kristiansen, Jun Wang, Jian Han, Lennart Hammarström, Qiang Pan-Hammarström
The dietary pattern can influence the immune system directly, but may also modulate it indirectly by regulating the gut microbiota. Here, we investigated the effect of a 3-months lacto-ovo-vegetarian diet on the diversity of gut microbiota and the immune system in healthy omnivorous volunteers, using high-throughput sequencing technologies. The short-term vegetarian diet did not have any major effect on the diversity of the immune system and the overall composition of the metagenome. The prevalence of bacterial genera/species with known beneficial effects on the intestine, including butyrate-producers and probiotic species and the balance of autoimmune-related variable genes/families were, however, altered in the short-term vegetarians...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29743177/hypomorphic-rag1-mutations-alter-the-pre-immune-repertoire-at-early-stages-of-lymphoid-development
#6
Lisa M Ott de Bruin, Marita Bosticardo, Alessandro Barbieri, Sherry G Lin, Jared H Rowe, Pietro L Poliani, Kimberly Ching, Daniel Eriksson, Nils Landegren, Olle Kämpe, John P Manis, Luigi D Notarangelo
Hypomorphic RAG1 mutations allowing residual T and B cell development have been found in patients presenting with delayed-onset combined immune deficiency with granulomas and/or autoimmunity (CID-G/AI) and abnormalities of the peripheral T and B cell repertoire. To examine how hypomorphic Rag1 mutations affect the earliest stages of lymphocyte development, we used CRISPR/Cas9 to generate mouse models with equivalent mutations found in patients with CID-G/AI. Immunological characterization showed partial development of T and B lymphocytes, with persistence of naïve cells, preserved serum immunoglobulin, but impaired antibody responses and presence of autoantibodies, thereby recapitulating the phenotype seen in patients with CID-G/AI...
May 9, 2018: Blood
https://www.readbyqxmd.com/read/29740455/sequence-based-discovery-demonstrates-that-fixed-light-chain-human-transgenic-rats-produce-a-diverse-repertoire-of-antigen-specific-antibodies
#7
Katherine E Harris, Shelley Force Aldred, Laura M Davison, Heather Anne N Ogana, Andrew Boudreau, Marianne Brüggemann, Michael Osborn, Biao Ma, Benjamin Buelow, Starlynn C Clarke, Kevin H Dang, Suhasini Iyer, Brett Jorgensen, Duy T Pham, Payal P Pratap, Udaya S Rangaswamy, Ute Schellenberger, Wim C van Schooten, Harshad S Ugamraj, Omid Vafa, Roland Buelow, Nathan D Trinklein
We created a novel transgenic rat that expresses human antibodies comprising a diverse repertoire of heavy chains with a single common rearranged kappa light chain (IgKV3-15-JK1). This fixed light chain animal, called OmniFlic, presents a unique system for human therapeutic antibody discovery and a model to study heavy chain repertoire diversity in the context of a constant light chain. The purpose of this study was to analyze heavy chain variable gene usage, clonotype diversity, and to describe the sequence characteristics of antigen-specific monoclonal antibodies (mAbs) isolated from immunized OmniFlic animals...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29735481/simultaneous-presence-of-non-and-highly-mutated-keyhole-limpet-hemocyanin-klh-specific-plasmablasts-early-after-primary-klh-immunization-suggests-cross-reactive-memory-b-cell-activation
#8
Claudia Giesecke, Tim Meyer, Pawel Durek, Jochen Maul, Jan Preiß, Joannes F M Jacobs, Andreas Thiel, Andreas Radbruch, Reiner Ullrich, Thomas Dörner
There are currently limited insights into the progression of human primary humoral immunity despite numerous studies in experimental models. In this study, we analyzed a primary and related secondary parenteral keyhole limpet hemocyanin (KLH) immunization in five human adults. The primary challenge elicited discordant KLH-specific serum and blood effector B cell responses (i.e., dominant serum KLH-specific IgG and IgM levels versus dominant KLH-specific IgA plasmablast frequencies). Single-cell IgH sequencing revealed early appearance of highly (>15 mutations) mutated circulating KLH-specific plasmablasts 2 wk after primary KLH immunization, with simultaneous KLH-specific plasmablasts carrying non- and low-mutated IgH sequences...
May 7, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29730603/vedolizumab-is-associated-with-changes-in-innate-rather-than-adaptive-immunity-in-patients-with-inflammatory-bowel-disease
#9
Sebastian Zeissig, Elisa Rosati, C Marie Dowds, Konrad Aden, Johannes Bethge, Berenice Schulte, Wei Hung Pan, Neha Mishra, Maaz Zuhayra, Marlies Marx, Maren Paulsen, Anne Strigli, Claudio Conrad, Dörthe Schuldt, Anupam Sinha, Henriette Ebsen, Sabin-Christin Kornell, Susanna Nikolaus, Alexander Arlt, Dieter Kabelitz, Mark Ellrichmann, Ulf Lützen, Philip C Rosenstiel, Andre Franke, Stefan Schreiber
OBJECTIVE: Vedolizumab, a monoclonal antibody directed against the integrin heterodimer α4β7, is approved for the treatment of Crohn's disease and ulcerative colitis. The efficacy of vedolizumab has been suggested to result from inhibition of intestinal T cell trafficking although human data to support this conclusion are scarce. We therefore performed a comprehensive analysis of vedolizumab-induced alterations in mucosal and systemic immunity in patients with inflammatory bowel disease (IBD), using anti-inflammatory therapy with the TNFα antibody infliximab as control...
May 5, 2018: Gut
https://www.readbyqxmd.com/read/29721371/complimentary-mechanisms-of-dual-checkpoint-blockade-expand-unique-t-cell-repertoires-and-activate-adaptive-anti-tumor-immunity-in-triple-negative-breast-tumors
#10
Erika J Crosby, Junping Wei, Xiao Yi Yang, Gangjun Lei, Tao Wang, Cong-Xiao Liu, Pankaj Agarwal, Alan J Korman, Michael A Morse, Kenneth Gouin, Simon R V Knott, H Kim Lyerly, Zachary C Hartman
Triple-negative breast cancer (TNBC) is an aggressive and molecularly diverse breast cancer subtype typified by the presence of p53 mutations (∼80%), elevated immune gene signatures and neoantigen expression, as well as the presence of tumor infiltrating lymphocytes (TILs). As these factors are hypothesized to be strong immunologic prerequisites for the use of immune checkpoint blockade (ICB) antibodies, multiple clinical trials testing single ICBs have advanced to Phase III, with early indications of heterogeneous response rates of <20% to anti-PD1 and anti-PDL1 ICB...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29720665/the-human-v%C3%AE-2-t-cell-compartment-comprises-distinct-innate-like-v%C3%AE-9-and-adaptive-v%C3%AE-9-subsets
#11
Martin S Davey, Carrie R Willcox, Stuart Hunter, Sofya A Kasatskaya, Ester B M Remmerswaal, Mahboob Salim, Fiyaz Mohammed, Frederike J Bemelman, Dmitriy M Chudakov, Ye H Oo, Benjamin E Willcox
Vδ2+ T cells form the predominant human γδ T-cell population in peripheral blood and mediate T-cell receptor (TCR)-dependent anti-microbial and anti-tumour immunity. Here we show that the Vδ2+ compartment comprises both innate-like and adaptive subsets. Vγ9+ Vδ2+ T cells display semi-invariant TCR repertoires, featuring public Vγ9 TCR sequences equivalent in cord and adult blood. By contrast, we also identify a separate, Vγ9- Vδ2+ T-cell subset that typically has a CD27hi CCR7+ CD28+ IL-7Rα+ naive-like phenotype and a diverse TCR repertoire, however in response to viral infection, undergoes clonal expansion and differentiation to a CD27lo CD45RA+ CX3 CR1+ granzymeA/B+ effector phenotype...
May 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29709038/hcmv-triggers-frequent-and-persistent-ul40-specific-unconventional-hla-e-restricted-cd8-t-cell-responses-with-potential-autologous-and-allogeneic-peptide-recognition
#12
Nicolas Jouand, Céline Bressollette-Bodin, Nathalie Gérard, Magali Giral, Pierrick Guérif, Audrey Rodallec, Romain Oger, Tiphaine Parrot, Mathilde Allard, Anne Cesbron-Gautier, Nadine Gervois, Béatrice Charreau
Immune response against human cytomegalovirus (HCMV) includes a set of persistent cytotoxic NK and CD8 T cells devoted to eliminate infected cells and to prevent reactivation. CD8 T cells against HCMV antigens (pp65, IE1) presented by HLA class-I molecules are well characterized and they associate with efficient virus control. HLA-E-restricted CD8 T cells targeting HCMV UL40 signal peptides (HLA-EUL40) have recently emerged as a non-conventional T-cell response also observed in some hosts. The occurrence, specificity and features of HLA-EUL40 CD8 T-cell responses remain mostly unknown...
April 30, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29704254/intrahepatic-t-cell-receptor-%C3%AE-immune-repertoire-is-essential-for-liver-regeneration
#13
Qing Liang, Zeyuan Liu, Chao Zhu, Bin Wang, Xiaoke Liu, Yanan Yang, Xue Lv, Haiyu Mu, Kejia Wang
T lymphocytes synergize with the cellular immune system to promote hepatocyte regeneration. The T cell receptor (TCR) immune repertoire is closely associated with the host immune response and regenerative proliferation. High-throughput sequencing of TCR provides deep insight into monitoring the immune microenvironment. Here, we aimed to determine the role of the TCRβ immune repertoire in liver regeneration. We investigated the hepatic regeneration in TCRβ chain-deficient (Tcrb-/- ) mice by two-thirds partial hepatectomy (PHx) method...
April 27, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29703216/simple-paired-heavy-and-light-chain-antibody-repertoire-sequencing-using-endoplasmic-reticulum-microsomes
#14
Praneeth Reddy Devulapally, Jörg Bürger, Thorsten Mielke, Zoltán Konthur, Hans Lehrach, Marie-Laure Yaspo, Jörn Glökler, Hans-Jörg Warnatz
Existing methods for paired antibody heavy- and light-chain repertoire sequencing rely on specialized equipment and are limited by their commercial availability and high costs. Here, we report a novel simple and cost-effective emulsion-based single-cell paired antibody repertoire sequencing method that employs only basic laboratory equipment. We performed a proof-of-concept using mixed mouse hybridoma cells and we also showed that our method can be used for discovery of novel antigen-specific monoclonal antibodies by sequencing human CD19+ B cell IgM and IgG repertoires isolated from peripheral whole blood before and seven days after Td (Tetanus toxoid/Diphtheria toxoid) booster immunization...
April 27, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29686053/identification-of-a-transcriptionally-forward-%C3%AE-gene-and-two-%C3%AF-genes-within-the-pigeon-columba-livia-igh-gene-locus
#15
Tian Huang, Xifeng Wang, Run Si, Hao Chi, Binyue Han, Haitang Han, Gengsheng Cao, Yaofeng Zhao
Compared with mammals, the bird Ig genetic system relies on gene conversion to create an Ab repertoire, with inversion of the IgA-encoding gene and very few cases of Ig subclass diversification. Although gene conversion has been studied intensively, class-switch recombination, a mechanism by which the IgH C region is exchanged, has rarely been investigated in birds. In this study, based on the published genome of pigeon ( Columba livia ) and high-throughput transcriptome sequencing of immune-related tissues, we identified a transcriptionally forward α gene and found that the pigeon IgH gene locus is arranged as μ-α-υ1-υ2...
April 23, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29685220/a-t4virus-prevents-biofilm-formation-by-trueperella-pyogenes
#16
Vinícius da Silva Duarte, Roberto Sousa Dias, Andrew M Kropinski, André da Silva Xavier, Camila Geovana Ferro, Pedro M P Vidigal, Cynthia Canedo da Silva, Sérgio Oliveira de Paula
Trueperella pyogenes is an opportunistic pathogen of many animal species. It causes economic losses worldwide, through mastitis, metritis and mainly endometritis in dairy cows. The ability of this bacterium to form biofilms is implicated in chronic infections through hampering immune system recognition and antibiotic penetration. Since it is difficult to eradicate T. pyogenes infections with antibiotics, phage therapy presents itself as a non-toxic, effective and economically viable alternative. The present study evaluated the use of the bacteriophage vB_EcoM-UFV13 (UFV13) in the prevention of T...
May 2018: Veterinary Microbiology
https://www.readbyqxmd.com/read/29684201/dysregulation-of-epstein-barr-virus-infection-in-hypomorphic-zap70-mutation
#17
Akihiro Hoshino, Takehiro Takashima, Kenichi Yoshida, Akira Morimoto, Yuta Kawahara, Tzu-Wen Yeh, Tsubasa Okano, Motoi Yamashita, Noriko Mitsuiki, Kohsuke Imai, Takashi Sakatani, Atsuko Nakazawa, Yusuke Okuno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Seiji Kojima, Tomohiro Morio, Hirokazu Kanegane
Background: Some patients with genetic defects develop Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD)/lymphoma as the main feature. Hypomophic mutations can cause different clinical and laboratory manifestations from null mutations in the same genes. Methods: We sought to describe the clinical and immunologic phenotype of a 21-month-old boy having EBV-associated LPD who was in good health till then. A genetic and immunologic analysis was performed...
April 19, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29669837/amino-acid-substitutions-within-hla-b-27-restricted-t-cell-epitopes-prevent-recognition-by-hepatitis-delta-virus-specific-cd8-t-cells
#18
Hadi Karimzadeh, Muthamia M Kiraithe, Anna D Kosinska, Manuel Glaser, Melanie Fiedler, Valerie Oberhardt, Elahe Salimi Alizei, Maike Hofmann, Juk Yee Mok, Melanie Nguyen, Wim J E van Esch, Bettina Budeus, Jan Grabowski, Maria Homs, Antonella Olivero, Hossein Keyvani, Francisco Rodríguez-Frías, David Tabernero, Maria Buti, Andreas Heinold, Seyed Moayed Alavian, Tanja Bauer, Julian Schulze Zur Wiesch, Bijan Raziorrouh, Daniel Hoffmann, Antonina Smedile, Mario Rizzetto, Heiner Wedemeyer, Jörg Timm, Iris Antes, Christoph Neumann-Haefelin, Ulrike Protzer, Michael Roggendorf
Virus-specific CD8 T-cell response seems to play a significant role in the outcome of hepatitis delta virus (HDV) infection. However, the HDV-specific T-cell epitope repertoire and mechanisms of CD8 T-cell failure in HDV infection have merely been characterized. We therefore aimed to characterize HDV-specific CD8 T cell epitopes and the impact of viral mutations on immune escape. In this study, we predicted peptide epitopes binding the most frequent HLA types and assessed their HLA binding capacity. These epitopes were characterized in HDV-infected patients by intracellular IFN-γ staining...
April 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29669518/irprofiler-a-software-toolbox-for-high-throughput-immune-receptor-profiling
#19
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
https://www.readbyqxmd.com/read/29668996/brepertoire-a-user-friendly-web-server-for-analysing-antibody-repertoire-data
#20
Christian Margreitter, Hui-Chun Lu, Catherine Townsend, Alexander Stewart, Deborah K Dunn-Walters, Franca Fraternali
Antibody repertoire analysis by high throughput sequencing is now widely used, but a persisting challenge is enabling immunologists to explore their data to discover discriminating repertoire features for their own particular investigations. Computational methods are necessary for large-scale evaluation of antibody properties. We have developed BRepertoire, a suite of user-friendly web-based software tools for large-scale statistical analyses of repertoire data. The software is able to use data preprocessed by IMGT, and performs statistical and comparative analyses with versatile plotting options...
April 14, 2018: Nucleic Acids Research
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