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Immune repertoire sequencing

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https://www.readbyqxmd.com/read/28818634/mining-na%C3%A3-ve-rabbit-antibody-repertoires-by-phage-display-for-monoclonal-antibodies-of-therapeutic-utility
#1
Haiyong Peng, Thomas Nerreter, Jing Chang, Junpeng Qi, Xiuling Li, Pabalu Karunadharma, Gustavo Martinez, Mohammad Fallahi, Jo Soden, Jim Freeth, Roger R Beerli, Ulf Grawunder, Michael Hudecek, Christoph Rader
Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but in some cases also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity...
August 14, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28813462/a-comprehensive-profiling-of-t-and-b-lymphocyte-receptor-repertoires-from-a-chinese-origin-rhesus-macaque-by-high-throughput-sequencing
#2
Longfei Fu, Xinyang Li, Wei Zhang, Changxi Wang, Jinghua Wu, Huanming Yang, Jian Wang, Xiao Liu
Due to the close genetic background, high similarity of physiology, and susceptibility to infectious and metabolic diseases with humans, rhesus macaques have been widely used as an important animal model in biomedical research, especially in the study of vaccine development and human immune-related diseases. In recent years, high-throughput sequencing based immune repertoire sequencing (IR-SEQ) has become a powerful tool to study the dynamic adaptive immune responses. Several previous studies had analyzed the responses of B cells to HIV-1 trimer vaccine or T cell repertoire of rhesus macaques using this technique, however, there are little studies that had performed a comprehensive analysis of immune repertoire of rhesus macaques, including T and B lymphocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28811963/characterization-of-the-cryoablation-induced-immune-response-in-kidney-cancer-patients
#3
Taigo Kato, Tomoyuki Iwasaki, Motohide Uemura, Akira Nagahara, Hiroki Higashihara, Keigo Osuga, Yuji Ikeda, Kazuma Kiyotani, Jae-Hyun Park, Norio Nonomura, Yusuke Nakamura
Cryoablation is one of treatment modalities for kidney cancer and is expected to induce strong local immune responses as well as systemic T-cell-mediated immune reactions that may lead to the regression of distant metastatic lesions. Thus, the characterization of T cell repertoire and immune environment in tumors before and after treatment should contribute to the better understanding of the cryoablation-induced anticancer immune responses. In this study, we collected tumor tissues from 22 kidney cancer patients, before cryoablation and at 3 mo after cryoablation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28803690/new-insights-into-non-conventional-epitopes-as-t-cell-targets-the-missing-link-for-breaking-immune-tolerance-in-autoimmune-disease
#4
REVIEW
James Harbige, Martin Eichmann, Mark Peakman
The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple mechanisms through which non-germline encoded sequences can give rise to these non-conventional epitopes which in turn engage the immune system as T cell targets. In particular, where these modifications alter the rules of epitope engagement with MHC molecules, such non-conventional epitopes offer a persuasive explanation for associations between specific HLA alleles and autoimmune diseases...
August 10, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28798410/a-novel-signature-for-stratifying-the-molecular-heterogeneity-of-the-tissue-infiltrating-t-cell-receptor-repertoire-reflects-gastric-cancer-prognosis
#5
Manchao Kuang, Jieyao Cheng, Chengli Zhang, Lin Feng, Xue Xu, Yajing Zhang, Ming Zu, Jianfang Cui, Hang Yu, Kaitai Zhang, Aiming Yang, Shujun Cheng
Many basic properties of the T-cell receptor (TCR) repertoire require clarification, and the changes occurring in the TCR repertoire during carcinogenesis, especially during precancerous stages, remain unclear. This study used deep sequencing analyses to examine 41 gastric tissue samples at different pathological stages, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, early gastric cancer and matched adjacent tissues, to define the characteristics of the infiltrating TCRβ repertoire during gastric carcinogenesis...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28782508/circulating-and-tissue-resident-cd4-t-cells-with-reactivity-to-intestinal-microbiota-are-abundant-in-healthy-individuals-and-function-is-altered-during-inflammation
#6
Ahmed N Hegazy, Nathaniel R West, Michael J T Stubbington, Emily Wendt, Kim I M Suijker, Angeliki Datsi, Sebastien This, Camille Danne, Suzanne Campion, Sylvia H Duncan, Benjamin M J Owens, Holm H Uhlig, Andrew McMichael, Andreas Bergthaler, Sarah A Teichmann, Satish Keshav, Fiona Powrie
BACKGROUND & AIMS: Interactions between commensal microbes and the immune system are tightly regulated and maintain intestinal homeostasis, but little is known about these interactions in humans. We investigated responses of human CD4(+) T cells to the intestinal microbiota. We measured the abundance of T cells in circulation and intestinal tissues that respond to intestinal microbes and determined their clonal diversity. We also assessed their functional phenotypes and effects on intestinal resident cell populations, and studied alterations in microbe-reactive T cells in patients with chronic intestinal inflammation...
August 3, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28761058/heterogeneity-of-tumor-infiltrating-lymphocytes-ascribed-to-local-immune-status-rather-than-neoantigens-by-multi-omics-analysis-of-glioblastoma-multiforme
#7
Lin Feng, Haipeng Qian, Xuexin Yu, Kan Liu, Ting Xiao, Chengli Zhang, Manchao Kuang, Shujun Cheng, Xueji Li, Jinghai Wan, Kaitai Zhang
Hypothetically, intratumoral genomic heterogeneity has the potential to foster tumor-infiltrating lymphocyte (TIL) diversity; however, no study has directly tested this hypothesis by simultaneously investigating somatic mutations, TIL diversity, and immune response activity. Thus, we performed whole-exome sequencing, immune repertoire sequencing and gene expression on ten spatially separated tumor samples obtained from two tumor masses excised from a glioblastoma multiforme (GBM) patient, and we included peripheral blood as control...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28759640/t-dependent-b-cell-responses-to-plasmodium-induce-antibodies-that-form-a-high-avidity-multivalent-complex-with-the-circumsporozoite-protein
#8
Camilla R Fisher, Henry J Sutton, Joe A Kaczmarski, Hayley A McNamara, Ben Clifton, Joshua Mitchell, Yeping Cai, Johanna N Dups, Nicholas J D'Arcy, Mandeep Singh, Aaron Chuah, Thomas S Peat, Colin J Jackson, Ian A Cockburn
The repeat region of the Plasmodium falciparum circumsporozoite protein (CSP) is a major vaccine antigen because it can be targeted by parasite neutralizing antibodies; however, little is known about this interaction. We used isothermal titration calorimetry, X-ray crystallography and mutagenesis-validated modeling to analyze the binding of a murine neutralizing antibody to Plasmodium falciparum CSP. Strikingly, we found that the repeat region of CSP is bound by multiple antibodies. This repeating pattern allows multiple weak interactions of single FAB domains to accumulate and yield a complex with a dissociation constant in the low nM range...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28759253/differential-recognition-of-mtb-specific-epitopes-as-a-function-of-tuberculosis-disease-history
#9
Thomas J Scriba, Chelsea Carpenter, Sebastian Carrasco Pro, John Sidney, Munyaradzi Musvosvi, Virginie Rozot, Grégory Seumois, Sandy L Rosales, Pandurangan Vijayanand, Delia Goletti, Edward Makgotlho, Willem Hanekom, Mark Hatherill, Bjoern Peters, Alessandro Sette, Cecilia S Lindestam Arlehamn
RATIONALE: Individuals with a history of tuberculosis disease are at elevated risk of disease recurrance. The underlying cause is not known, but one explanation is that previous disease results in less effective immunity against Mycobacterium tuberculosis (Mtb). OBJECTIVE: We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection (LTBI) differs as a function of previous diagnosis of active tuberculosis (TB) disease...
July 31, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28756139/a-universal-phage-display-system-for-the-seamless-construction-of-fab-libraries
#10
Renae S Nelson, Philippe Valadon
The construction of Fab phage libraries requires the cloning of domains from both the light and the heavy chain of antibodies. Despite the advent of powerful strategies such as splicing-by-overlap extension PCR, obtaining high quality libraries with excellent coverage remains challenging. Here, we explored the use of type IIS restriction enzymes for the seamless cloning of Fab libraries. We analyzed human, murine and rabbit germline antibody repertoires and identified combinations of restriction enzymes that exhibit very few or no recognition sites in the antibody sequences...
July 26, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28747495/hiv-and-siv-maintain-high-levels-of-infectivity-in-the-complete-absence-of-mucin-type-o-glycosylation
#11
James M Termini, Elizabeth S Church, Zachary A Silver, Stuart M Haslam, Anne Dell, Ronald C Desrosiers
A highly conserved threonine near the C-terminus of gp120 of HIV and SIV was investigated for its contributions to envelope protein function and virion infectivity. When this highly conserved Thr residue was substituted with anything other than serine (the other amino acid that can accept O-glycosylation), the resulting virus was non-infectious. We found that this Thr was critical for the association of gp120 with the virion and that amino acid substitution increased the amount of dissociated gp120 in the cell culture supernatant...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28747151/comparative-analysis-of-targeted-long-read-sequencing-approaches-for-characterization-of-a-plant-s-immune-receptor-repertoire
#12
Michael Giolai, Pirita Paajanen, Walter Verweij, Kamil Witek, Jonathan D G Jones, Matthew D Clark
BACKGROUND: The Oxford Nanopore Technologies MinION™ sequencer is a small, portable, low cost device that is accessible to labs of all sizes and attractive for in-the-field sequencing experiments. Selective breeding of crops has led to a reduction in genetic diversity, and wild relatives are a key source of new genetic resistance to pathogens, usually via NLR immune receptor-encoding genes. Recent studies have demonstrated how crop NLR repertoires can be targeted for sequencing on Illumina or PacBio (RenSeq) and the specific gene conveying pathogen resistance identified...
July 26, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28731407/t-cell-receptor-repertoires-of-mice-and-humans-are-clustered-in-similarity-networks-around-conserved-public-cdr3-sequences
#13
Asaf Madi, Asaf Poran, Eric Shifrut, Shlomit Reich-Zeliger, Erez Greenstein, Irena Zaretsky, Tomer Arnon, Francois Van Laethem, Alfred Singer, Jinghua Lu, Peter D Sun, Irun R Cohen, Nir Friedman
Diversity of T cell receptor (TCR) repertoires, generated by somatic DNA rearrangements, is central to immune system function. However, the level of sequence similarity of TCR repertoires within and between species has not been characterized. Using network analysis of high-throughput TCR sequencing data, we found that abundant CDR3-TCRβ sequences were clustered within networks generated by sequence similarity. We discovered a substantial number of public CDR3-TCRβ segments that were identical in mice and humans...
July 21, 2017: ELife
https://www.readbyqxmd.com/read/28720171/pacbio-assembly-of-a-plasmodium-knowlesi-genome-sequence-with-hi-c-correction-and-manual-annotation-of-the-sicavar-gene-family
#14
S A Lapp, J A Geraldo, J-T Chien, F Ay, S B Pakala, G Batugedara, J Humphrey, J D DeBARRY, K G Le Roch, M R Galinski, J C Kissinger
Plasmodium knowlesi has risen in importance as a zoonotic parasite that has been causing regular episodes of malaria throughout South East Asia. The P. knowlesi genome sequence generated in 2008 highlighted and confirmed many similarities and differences in Plasmodium species, including a global view of several multigene families, such as the large SICAvar multigene family encoding the variant antigens known as the schizont-infected cell agglutination proteins. However, repetitive DNA sequences are the bane of any genome project, and this and other Plasmodium genome projects have not been immune to the gaps, rearrangements and other pitfalls created by these genomic features...
July 19, 2017: Parasitology
https://www.readbyqxmd.com/read/28706301/a-haystack-heuristic-for-autoimmune-disease-biomarker-discovery-using-next-gen-immune-repertoire-sequencing-data
#15
Leonard Apeltsin, Shengzhi Wang, H-Christian von Büdingen, Marina Sirota
Large-scale DNA sequencing of immunological repertoires offers an opportunity for the discovery of novel biomarkers for autoimmune disease. Available bioinformatics techniques however, are not adequately suited for elucidating possible biomarker candidates from within large immunosequencing datasets due to unsatisfactory scalability and sensitivity. Here, we present the Haystack Heuristic, an algorithm customized to computationally extract disease-associated motifs from next-generation-sequenced repertoires by contrasting disease and healthy subjects...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28706143/integrated-analysis-of-somatic-mutations-and-immune-microenvironment-of-multiple-regions-in-breast-cancers
#16
Taigo Kato, Jae-Hyun Park, Kazuma Kiyotani, Yuji Ikeda, Yasuo Miyoshi, Yusuke Nakamura
Next-generation sequencing technology enables us to analyze the complexity of intra- and inter-tumoral heterogeneity, which may influence to prognosis of cancer patients. In this study, we collected surgically-resected tumor tissues from five breast cancer patients and characterized three different portions of individual tumors through somatic mutation analysis by whole exome sequencing, T cell receptor beta (TCRB) repertoire analysis of tumor-infiltrating lymphocytes (TILs), and the expression analysis of immune-related genes at 15 different sites...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28705718/antimicrobial-peptide-repertoire-of-thitarodes-armoricanus-a-host-species-of-ophiocordyceps-sinensis-predicted-based-on-de-novo-transcriptome-sequencing-and-analysis
#17
Min Wang, Xianda Hu
Ophiocordyceps sinensis is an entomopathogenic fungus that parasitizes the larvae of ghost moths. The fungus-caterpillar complex resulting from fungal parasitism is a medicinally and economically important traditional Chinese medicine famous for its tonic, aphrodisiac and immunomodulatory activity. Antimicrobial peptides (AMPs), which play predominant roles in responding to infection of pathogenic microorganisms in the immune system of ghost moths, may remain behind the fungus-caterpillar complex. Thitarodes armoricanus, as a widely distributed ghost moth on the Tibetan Plateau, is the first reported and one of the most common host insects of O...
July 11, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28698278/on-the-origin-of-reverse-transcriptase-using-crispr-cas-systems-and-their-hyperdiverse-enigmatic-spacer-repertoires
#18
Sukrit Silas, Kira S Makarova, Sergey Shmakov, David Páez-Espino, Georg Mohr, Yi Liu, Michelle Davison, Simon Roux, Siddharth R Krishnamurthy, Becky Xu Hua Fu, Loren L Hansen, David Wang, Matthew B Sullivan, Andrew Millard, Martha R Clokie, Devaki Bhaya, Alan M Lambowitz, Nikos C Kyrpides, Eugene V Koonin, Andrew Z Fire
Cas1 integrase is the key enzyme of the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas adaptation module that mediates acquisition of spacers derived from foreign DNA by CRISPR arrays. In diverse bacteria, the cas1 gene is fused (or adjacent) to a gene encoding a reverse transcriptase (RT) related to group II intron RTs. An RT-Cas1 fusion protein has been recently shown to enable acquisition of CRISPR spacers from RNA. Phylogenetic analysis of the CRISPR-associated RTs demonstrates monophyly of the RT-Cas1 fusion, and coevolution of the RT and Cas1 domains...
July 11, 2017: MBio
https://www.readbyqxmd.com/read/28697819/functional-characterization-of-single-domain-cystatin-like-cysteine-proteinase-inhibitors-expressed-by-the-trematode-fasciola-hepatica
#19
Martín Cancela, Ileana Corvo, Edileuza DA Silva, Aline Teichmann, Leda Roche, Alvaro Díaz, José Fransisco Tort, Henrique B Ferreira, Arnaldo Zaha
Cystatins are small, phylogenetically conserved proteins that are tight-binding inhibitors of cysteine proteinases. The liver fluke Fasciola hepatica uses a diverse set of cysteine proteinases of the papain superfamily for host invasion, immune evasion and nutrition, but little is known about the regulation of these enzymes. The aim of this work is to characterize the cystatin repertoire of F. hepatica. For this purpose, we first surveyed the available sequence databases, identifying three different F. hepatica single-domain cystatins...
July 12, 2017: Parasitology
https://www.readbyqxmd.com/read/28697735/v-j-combinations-of-t-cell-receptor-predict-responses-to-erythropoietin-in-end-stage-renal-disease-patients
#20
Henry Sung-Ching Wong, Che-Mai Chang, Chih-Chin Kao, Yu-Wen Hsu, Xiao Liu, Wen-Chang Chang, Mai-Szu Wu, Wei-Chiao Chang
BACKGROUND: Anemia is common among end-stage renal disease (ESRD) patients who undergone hemodialysis. The total reduction of red blood cell (RBC) count is associated with poor prognosis in these patients. Although erythropoietin (EPO) has been used as an effective treatment for ESRD patients with anemia, a large number of patients still present poor responses to EPO treatment. METHODS: We measured T-cell receptor sequencing profiles, including length of complementarity-deteremining region 3 (CDR3), intra- and inter-group (EPO resistant vs...
July 11, 2017: Journal of Biomedical Science
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