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Immune repertoire sequencing

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https://www.readbyqxmd.com/read/28637924/vp4-and-vp7-specific-antibodies-mediate-heterotypic-immunity-to-rotavirus-in-humans
#1
Nitya Nair, Ningguo Feng, Lisa K Blum, Mrinmoy Sanyal, Siyuan Ding, Baoming Jiang, Adrish Sen, John M Morton, Xiao-Song He, William H Robinson, Harry B Greenberg
Human rotaviruses (RVs) are the leading cause of severe diarrhea in young children worldwide. The molecular mechanisms underlying the rapid induction of heterotypic protective immunity to RV, which provides the basis for the efficacy of licensed monovalent RV vaccines, have remained unknown for more than 30 years. We used RV-specific single cell-sorted intestinal B cells from human adults, barcode-based deep sequencing of antibody repertoires, monoclonal antibody expression, and serologic and functional characterization to demonstrate that infection-induced heterotypic immunoglobulins (Igs) primarily directed to VP5*, the stalk region of the RV attachment protein, VP4, are able to mediate heterotypic protective immunity...
June 21, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28636592/quantifiable-predictive-features-define-epitope-specific-t-cell-receptor-repertoires
#2
Pradyot Dash, Andrew J Fiore-Gartland, Tomer Hertz, George C Wang, Shalini Sharma, Aisha Souquette, Jeremy Chase Crawford, E Bridie Clemens, Thi H O Nguyen, Katherine Kedzierska, Nicole L La Gruta, Philip Bradley, Paul G Thomas
T cells are defined by a heterodimeric surface receptor, the T cell receptor (TCR), that mediates recognition of pathogen-associated epitopes through interactions with peptide and major histocompatibility complexes (pMHCs). TCRs are generated by genomic rearrangement of the germline TCR locus, a process termed V(D)J recombination, that has the potential to generate marked diversity of TCRs (estimated to range from 10(15) (ref. 1) to as high as 10(61) (ref. 2) possible receptors). Despite this potential diversity, TCRs from T cells that recognize the same pMHC epitope often share conserved sequence features, suggesting that it may be possible to predictively model epitope specificity...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28628037/alloimmune-t-cells-in-transplantation
#3
Susan DeWolf, Megan Sykes
Alloimmune T cells are central mediators of rejection and graft-versus-host disease in both solid organ and hematopoietic stem cell transplantation. Unique among immune responses in terms of its strength and diversity, the T cell alloresponse reflects extensive genetic polymorphisms between allogeneic donors and recipients, most prominently within the major histocompatibility complex (MHC), which encodes human leukocyte antigens (HLAs) in humans. The repertoire of alloreactive T cell clones is distinct for every donor-recipient pair and includes potentially thousands of unique HLA/peptide specificities...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28621685/active-evolution-of-memory-b-cells-specific-to-viral-gh-gl-pul128-130-131-pentameric-complex-in-healthy-subjects-with-silent-human-cytomegalovirus-infection
#4
Lin Xia, Aimin Tang, Weixu Meng, Daniel C Freed, Linling He, Dai Wang, Fengsheng Li, Leike Li, Wei Xiong, Xun Gui, Robbie D Schultz, Haotai Chen, Xi He, Ryan Swoyer, Sha Ha, Yaping Liu, Charles D Morris, Yu Zhou, I-Ming Wang, Qinjian Zhao, Wenxin Luo, Ningshao Xia, Amy S Espeseth, Daria J Hazuda, Richard E Rupp, Alan D Barrett, Ningyan Zhang, Jiang Zhu, Tong-Ming Fu, Zhiqiang An
Human cytomegalovirus (HCMV) can cause life-threatening infection in immunosuppressed patients, and in utero infection that may lead to birth defects. No vaccine is currently available. HCMV infection in healthy subjects is generally asymptomatic, and virus persists as latent infection for life. Host immunity is effective against reactivation and super-infection with another strain. Thus, vaccine candidates able to elicit immune responses similar to those of natural infection may confer protection. Since neutralization is essential for prophylactic vaccines, it is important to understand how antiviral antibodies are developed in natural infection...
June 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620653/successive-annual-influenza-vaccination-induces-a-recurrent-oligoclonotypic-memory-response-in-circulating-t-follicular-helper-cells
#5
Ramin Sedaghat Herati, Alexander Muselman, Laura Vella, Bertram Bengsch, Kaela Parkhouse, Daniel Del Alcazar, Jonathan Kotzin, Susan A Doyle, Pablo Tebas, Scott E Hensley, Laura F Su, Kenneth E Schmader, E John Wherry
T follicular helper (Tfh) CD4 cells are crucial providers of B cell help during adaptive immune responses. A circulating population of CD4 T cells, termed cTfh, have similarity to lymphoid Tfh, can provide B cell help, and responded to influenza vaccination. However, it is unclear whether human vaccination-induced cTfh respond in an antigen-specific manner and whether they form long-lasting memory. Here, we identified a cTfh population that expressed multiple T cell activation markers and could be readily identified by coexpression of ICOS and CD38...
February 2017: Science Immunology
https://www.readbyqxmd.com/read/28620372/deep-sequencing-in-infectious-diseases-immune-and-pathogen-repertoires-for-the-improvement-of-patient-outcomes
#6
William F Burkholder, Evan W Newell, Michael Poidinger, Swaine Chen, Katja Fink
The inaugural workshop "Deep Sequencing in Infectious Diseases: Immune and Pathogen Repertoires for the Improvement of Patient Outcomes" was held in Singapore on 13-14 October 2016. The aim of the workshop was to discuss the latest trends in using high-throughput sequencing, bioinformatics, and allied technologies to analyze immune and pathogen repertoires and their interplay within the host, bringing together key international players in the field and Singapore-based researchers and clinician-scientists. The focus was in particular on the application of these technologies for the improvement of patient diagnosis, prognosis and treatment, and for other broad public health outcomes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28617221/identification-of-cancer-specific-motifs-in-mimotope-profiles-of-serum-antibody-repertoire
#7
Ekaterina Gerasimov, Alex Zelikovsky, Ion Măndoiu, Yurij Ionov
BACKGROUND: For fighting cancer, earlier detection is crucial. Circulating auto-antibodies produced by the patient's own immune system after exposure to cancer proteins are promising bio-markers for the early detection of cancer. Since an antibody recognizes not the whole antigen but 4-7 critical amino acids within the antigenic determinant (epitope), the whole proteome can be represented by a random peptide phage display library. This opens the possibility to develop an early cancer detection test based on a set of peptide sequences identified by comparing cancer patients' and healthy donors' global peptide profiles of antibody specificities...
June 7, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28610800/human-igg-repertoire-of-malaria-antigen-immunized-human-immune-system-his-mice
#8
Raquel Tayar Nogueira, Vincent Sahi, Jing Huang, Moriya Tsuji
Humanized mouse models present an important tool for preclinical evaluation of new vaccines and therapeutics. Here we show the human variable repertoire of antibody sequences cloned from a previously described human immune system (HIS) mouse model that possesses functional human CD4+ T cells and B cells, namely HIS-CD4/B mice. We sequenced variable IgG genes from single memory B-cell and plasma-cell sorted from splenocytes or whole blood lymphocytes of HIS-CD4/B mice that were vaccinated with a human plasmodial antigen, a recombinant Plasmodium falciparum circumsporozoite protein (rPfCSP)...
June 10, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28600290/high-throughput-single-cell-analysis-of-b-cell-receptor-usage-among-autoantigen-specific-plasma-cells-in-celiac-disease
#9
Bishnudeo Roy, Ralf S Neumann, Omri Snir, Rasmus Iversen, Geir Kjetil Sandve, Knut E A Lundin, Ludvig M Sollid
Characterization of Ag-specific BCR repertoires is essential for understanding disease mechanisms involving humoral immunity. This is optimally done by interrogation of paired H chain V region (VH) and L chain V region (VL) sequences of individual and Ag-specific B cells. By applying single-cell high-throughput sequencing on gut lesion plasma cells (PCs), we have analyzed the transglutaminase 2 (TG2)-specific VH:VL autoantibody repertoire of celiac disease (CD) patients. Autoantibodies against TG2 are a hallmark of CD, and anti-TG2 IgA-producing gut PCs accumulate in patients upon gluten ingestion...
June 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28599078/non-lesional-atopic-dermatitis-skin-shares-similar-t-cell-clones-with-lesional-tissues
#10
Patrick M Brunner, Ryan O Emerson, Christopher Tipton, Sandra Garcet, Saakshi Khattri, Israel Coats, James G Krueger, Emma Guttman-Yassky
BACKGROUND: Atopic dermatitis (AD) is characterized by robust immune activation. Various T-cell subsets, including Th2/Th22 cells, are increased in lesional and non-lesional skin. However, there is conflicting literature on the diversity of the T-cell receptor (TCR) repertoire in lesional AD, and its relation to non-lesional skin remains unclear. METHODS: We performed high-throughput deep sequencing of the β-TCR repertoire in 29 lesional and 19 non-lesional AD biopsies, compared to 6 healthy control and 6 cutaneous T-cell lymphoma (CTCL) samples from previously published cohorts...
June 9, 2017: Allergy
https://www.readbyqxmd.com/read/28592539/hiv-1-epitope-variability-is-associated-with-t-cell-receptor-repertoire-instability-and-breadth
#11
Arumugam Balamurugan, Deon Claiborne, Hwee L Ng, Otto O Yang
Mutational escape of HIV-1 from HIV-1-specific CD8(+) T lymphocytes (CTLs) is a major barrier for effective immune control. Each epitope typically is targeted by multiple clones with distinct T cell receptors (TCRs). While the clonal repertoire may be important for containing epitope variation, determinants of its composition are poorly understood. We investigate the clonal repertoire of 29 CTL responses against 23 HIV-1 epitopes longitudinally in nine chronically infected untreated subjects with plasma viremia <3000 RNA copies/ml over 17 to 179 weeks...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28566130/novel-approaches-to-analyze-immunoglobulin-repertoires
#12
REVIEW
Hedda Wardemann, Christian E Busse
Analysis of immunoglobulin (Ig) repertoires aims to comprehend Ig diversity with the goal of predicting humoral immune responses in the context of infection, vaccination, autoimmunity, and malignancies. The first next-generation sequencing (NGS) analyses of bulk B cell populations dramatically advanced sampling depth over previous low-throughput single-cell-based protocols, albeit at the expense of accuracy and loss of chain-pairing information. In recent years the field has substantially differentiated, with bulk analyses becoming more accurate while single-cell approaches have gained in throughput...
May 26, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28539440/uncovering-the-repertoire-of-endogenous-flaviviral-elements-in-aedes-mosquito-genomes
#13
Yasutsugu Suzuki, Lionel Frangeul, Laura B Dickson, Hervé Blanc, Yann Verdier, Joelle Vinh, Louis Lambrechts, Maria-Carla Saleh
Endogenous viral elements derived from non-retroviral RNA viruses were described in various animal genomes. Whether they have a biological function such as host immune protection against related viruses is a field of intense study. Here, we investigated the repertoire of endogenous flaviviral elements (EFVEs) in Aedes mosquitoes, the vectors of arboviruses such as dengue and chikungunya viruses. Previous studies identified three EFVEs from Ae. albopictus and one from Ae. aegypti cell lines. However, in-depth characterization of EFVEs in wild-type mosquito populations and individuals in vivo has not been performed...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28535950/aging-related-changes-in-human-t-cell-repertoire-over-20years-delineated-by-deep-sequencing-of-peripheral-t-cell-receptors
#14
Kengo Yoshida, John B Cologne, Kismet Cordova, Munechika Misumi, Mika Yamaoka, Seishi Kyoizumi, Tomonori Hayashi, Harlan Robins, Yoichiro Kusunoki
Recent deep sequencing studies on T-cell receptor (TCR) repertoire have provided robust data to characterize diversity of T-cell immune responsiveness to a wide variety of peptide antigens, including viral and tumor antigens. The human TCR repertoire declines with age, but this decline has not been fully investigated longitudinally in individuals. Using a deep sequencing approach, we analyzed TCRβ repertoires longitudinally over approximately 20years, with ages ranging from 23 to 50years at the start (23 to 65years overall), in peripheral-blood CD4 and CD8 T-cell populations that were collected and cryopreserved 3 times at intervals of approximately 10years from each of 6 healthy adults (3 men and 3 women)...
May 20, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28533222/fractionated-radiation-therapy-stimulates-anti-tumor-immunity-mediated-by-both-resident-and-infiltrating-polyclonal-t-cell-populations-when-combined-with-pd1-blockade
#15
Simon J Dovedi, Eleanor J Cheadle, Amy Popple, Edmund Poon, Michelle Morrow, Ross Stewart, Erik Yusko, Catherine Sanders, Marissa Vignali, Ryan Emerson, Harlan Robins, Robert W Wilkinson, Jamie Honeychurch, Timothy Illidge
Purpose: Radiotherapy (RT) is a highly effective anti-cancer treatment forming part of the standard of care for the majority of patients, but local and distal disease recurrence remains a major cause of mortality. RT is known to enhance tumor immunogenicity; however, the contribution and mechanisms of RT induced immune responses are unknown. <p>Experimental Design: The impact of low-dose fractionated RT (5 x 2 Gy) alone and in combination with αPD-1 mAb on the tumor microenvironment was evaluated by flow cytometry and next-generation sequencing (NGS) of the T-cell receptor (TCR)-repertoire...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28532760/research-techniques-made-simple-high-throughput-sequencing-of-the-t-cell-receptor
#16
Tiago R Matos, Menno A de Rie, Marcel B M Teunissen
High-throughput sequencing (HTS) of the T-cell receptor (TCR) is a rapidly advancing technique that allows sensitive and accurate identification and quantification of every distinct T-cell clone present within any biological sample. The relative frequency of each individual clone within the full T-cell repertoire can also be studied. HTS is essential to expand our knowledge on the diversity of the TCR repertoire in homeostasis or under pathologic conditions, as well as to understand the kinetics of antigen-specific T-cell responses that lead to protective immunity (i...
June 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28528860/purifying-selection-and-concerted-evolution-of-rna-sensing-toll-like-receptors-in-migratory-waders
#17
Nynke Raven, Simeon Lisovski, Marcel Klaassen, Nathan Lo, Thomas Madsen, Simon Y W Ho, Beata Ujvari
Migratory birds encounter a broad range of pathogens during their journeys, making them ideal models for studying immune gene evolution. Despite the potential value of these species to immunoecology and disease epidemiology, previous studies have typically focused on their adaptive immune gene repertoires. In this study, we examined the evolution of innate immune genes in three long-distance migratory waders (order Charadriiformes). We analysed two parts of the extracellular domains of two Toll-like receptors (TLR3 and TLR7) involved in virus recognition in the Sanderling (Calidris alba), Red-necked Stint (Calidris ruficollis), and Ruddy Turnstone (Arenaria interpres)...
May 18, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28520808/proteomic-analysis-of-biomphalaria-glabrata-plasma-proteins-with-binding-affinity-to-those-expressed-by-early-developing-larval-schistosoma-mansoni
#18
Xiao-Jun Wu, Nathalie Dinguirard, Grzegorz Sabat, Hong-di Lui, Laura Gonzalez, Michael Gehring, Utibe Bickham-Wright, Timothy P Yoshino
Interactions between early developing Schistosoma mansoni larval stages and the hemolymph of its snail intermediate host represent the first molecular encounter with the snail's immune system. To gain a more comprehensive understanding of this early parasite-host interaction, biotinylated sporocyst tegumental membrane (Mem) proteins and larval transformation proteins (LTP) were affixed to streptavidin-agarose beads and used as affinity matrices to enrich for larval-reactive plasma proteins from susceptible (NMRI) and resistant (BS-90) strains of the snail Biomphalaria glabrata...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28520789/antigen-specific-immunoglobulin-variable-region-sequencing-measures-humoral-immune-response-to-vaccination-in-the-equine-neonate
#19
Rebecca L Tallmadge, Steven C Miller, Stephen A Parry, Maria Julia B Felippe
The value of prophylactic neonatal vaccination is challenged by the interference of passively transferred maternal antibodies and immune competence at birth. Taken our previous studies on equine B cell ontogeny, we hypothesized that the equine neonate generates a diverse immunoglobulin repertoire in response to vaccination, independently of circulating maternal antibodies. In this study, equine neonates were vaccinated with 3 doses of keyhole limpet hemocyanin (KLH) or equine influenza vaccine, and humoral immune responses were assessed using antigen-specific serum antibodies and B cell Ig variable region sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/28517930/middle-down-193-nm-ultraviolet-photodissociation-for-unambiguous-antibody-identification-and-its-implications-for-immunoproteomic-analysis
#20
Victoria C Cotham, Andrew P Horton, Jiwon Lee, George Georgiou, Jennifer S Brodbelt
Mass spectrometry (MS) has emerged as a powerful tool within the growing field of immunoproteomics, which aims to understand antibody-mediated immunity at the molecular-level based on the direct determination of serological antibody repertoire. To date, these methods have relied on the use of high-resolution bottom-up proteomic strategies that require effective sampling and characterization of low abundance peptides derived from the antigen-binding domains of polyclonal antibody mixtures. Herein, we describe a method that uses restricted Lys-C enzymatic digestion to increase the average mass of proteolytic IgG peptides (≥4...
May 26, 2017: Analytical Chemistry
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