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Immune Repertoire

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https://read.qxmd.com/read/30772305/co-activation-of-macrophages-and-t-cells-contribute-to-chronic-gvhd-in-human-il-6-transgenic-humanised-mouse-model
#1
Rintaro Ono, Takashi Watanabe, Eiryo Kawakami, Makoto Iwasaki, Mariko Tomizawa-Murasawa, Masashi Matsuda, Yuho Najima, Shinsuke Takagi, Saera Fujiki, Rumi Sato, Yoshiki Mochizuki, Hisahiro Yoshida, Kaoru Sato, Hiromasa Yabe, Shunichi Kato, Yoriko Saito, Shuichi Taniguchi, Leonard D Shultz, Osamu Ohara, Masayuki Amagai, Haruhiko Koseki, Fumihiko Ishikawa
BACKGROUND: Graft-versus host disease (GVHD) is a complication of stem cell transplantation associated with significant morbidity and mortality. Non-specific immune-suppression, the mainstay of treatment, may result in immune-surveillance dysfunction and disease recurrence. METHODS: We created humanised mice model for chronic GVHD (cGVHD) by injecting cord blood (CB)-derived human CD34+ CD38- CD45RA- haematopoietic stem/progenitor cells (HSPCs) into hIL-6 transgenic NOD/SCID/Il2rgKO (NSG) newborns, and compared GVHD progression with NSG newborns receiving CB CD34- cells mimicking acute GVHD...
February 13, 2019: EBioMedicine
https://read.qxmd.com/read/30770409/the-early-proximal-%C3%AE-%C3%AE-tcr-signalosome-specifies-thymic-selection-outcome-through-a-quantitative-protein-interaction-network
#2
Steven C Neier, Alejandro Ferrer, Katelynn M Wilton, Stephen E P Smith, April M H Kelcher, Kevin D Pavelko, Jenna M Canfield, Tessa R Davis, Robert J Stiles, Zhenjun Chen, James McCluskey, Scott R Burrows, Jamie Rossjohn, Deanne M Hebrink, Eva M Carmona, Andrew H Limper, Dietmar J Kappes, Peter J Wettstein, Aaron J Johnson, Larry R Pease, Mark A Daniels, Claudia Neuhauser, Diana Gil, Adam G Schrum
During αβ T cell development, T cell antigen receptor (TCR) engagement transduces biochemical signals through a protein-protein interaction (PPI) network that dictates dichotomous cell fate decisions. It remains unclear how signal specificity is communicated, instructing either positive selection to advance cell differentiation or death by negative selection. Early signal discrimination might occur by PPI signatures differing qualitatively (customized, unique PPI combinations for each signal), quantitatively (graded amounts of a single PPI series), or kinetically (speed of PPI pathway progression)...
February 15, 2019: Science Immunology
https://read.qxmd.com/read/30769005/erap1-allotypes-impact-the-epitope-repertoire-of-virus-specific-cd8-t-cell-responses-in-acute-hepatitis-c-virus-infection
#3
Janine Kemming, Emma Reeves, Katja Nitschke, Vanessa Widmeier, Florian Emmerich, Tobias Hermle, Emma Gostick, Andreas Walker, Jörg Timm, David A Price, Maike Hofmann, Robert Thimme, Edward James, Christoph Neumann-Haefelin
BACKGROUND & AIMS: Endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms are linked with human leukocyte antigen (HLA) class I-associated autoinflammatory disorders, including ankylosing spondylitis and Behçet's disease. Disease-associated ERAP1 allotypes exhibit distinct functional properties, but it remains unclear how differential peptide trimming in vivo affects the repertoire of epitopes presented to CD8+ T cells. The aim of this study was to determine the impact of ERAP1 allotypes on the virus-specific CD8+ T cell epitope repertoire in an HLA-B*27:05+ individual with acute hepatitis C virus (HCV) infection...
February 12, 2019: Journal of Hepatology
https://read.qxmd.com/read/30768832/single-cell-immune-profiling-in-transplantation-research
#4
Lauren E Higdon, Steven Schaffert, Purvesh Khatri, Jonathan S Maltzman
Recently developed single-cell profiling technologies hold promise to provide new insights including analysis of population heterogeneity and linkage of antigen receptors with gene expression. These technologies produce complex data sets that require knowledge of bioinformatics for appropriate analysis. In this minireview, we discuss several single-cell immune profiling technologies for gene and protein expression, including cytometry by time-of-flight, RNA sequencing, and antigen receptor sequencing, as well as key considerations for analysis that apply to each...
February 15, 2019: American Journal of Transplantation
https://read.qxmd.com/read/30764863/systemic-translocation-of-staphylococcus-drives-autoantibody-production-in-hiv-disease
#5
Zhenwu Luo, Min Li, Yongxia Wu, Zhefeng Meng, Lisa Martin, Lumin Zhang, Elizabeth Ogunrinde, Zejun Zhou, Shenghui Qin, Zhuang Wan, Maria Anna Julia Westerink, Stephanie Warth, Hui Liu, Ping Jin, David Stroncek, Quan-Zhen Li, Ena Wang, Xueling Wu, Sonya L Heath, Zihai Li, Alexander V Alekseyenko, Wei Jiang
BACKGROUND: Increased autoreactive antibodies have been reported in HIV disease; however, the mechanism accounting for autoantibody induction in HIV remains unknown. RESULTS: Herein, we show that seasonal influenza vaccination induces autoantibody production (e.g., IgG anti-nuclear antibody (ANA) and anti-double-stranded DNA antibody (anti-dsDNA)) in some viral-suppressed antiretroviral therapy (ART)-treated HIV+ subjects, but not in healthy controls. These autoantibodies were not derived from antigen-specific B cells but from activated "bystander" B cells analyzed by single-cell assay and by study of purified polyclonal ANAs from plasma...
February 14, 2019: Microbiome
https://read.qxmd.com/read/30764544/early-pregnancy-human-decidua-is-enriched-with-activated-fully-differentiated-and-pro-inflammatory-gamma-delta-t-cells-with-diverse-tcr-repertoires
#6
Antonia Terzieva, Violeta Dimitrova, Lyubomir Djerov, Petya Dimitrova, Silvina Zapryanova, Iana Hristova, Ivaylo Vangelov, Tanya Dimova
Pregnancy is a state where high and stage-dependent plasticity of the maternal immune system is necessary in order to equilibrate between immunosuppression of harmful responses towards the fetus and ability to fight infections. TCR γδ cells have been implicated in the responses in infectious diseases, in the regulation of immune responses, and in tissue homeostasis and repair. The variety of functions makes γδ T cells a particularly interesting population during pregnancy. In this study, we investigated the proportion, phenotype and TCR γ and δ repertoires of γδ T cells at the maternal⁻fetal interface and in the blood of pregnant women using FACS, immunohistochemistry and spectratyping...
February 5, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30760926/high-frequency-of-shared-clonotypes-in-human-b-cell-receptor-repertoires
#7
Cinque Soto, Robin G Bombardi, Andre Branchizio, Nurgun Kose, Pranathi Matta, Alexander M Sevy, Robert S Sinkovits, Pavlo Gilchuk, Jessica A Finn, James E Crowe
The human genome contains approximately 20 thousand protein-coding genes1 , but the size of the collection of antigen receptors of the adaptive immune system that is generated by the recombination of gene segments with non-templated junctional additions (on B cells) is unknown-although it is certainly orders of magnitude larger. It has not been established whether individuals possess unique (or private) repertoires or substantial components of shared (or public) repertoires. Here we sequence recombined and expressed B cell receptor genes in several individuals to determine the size of their B cell receptor repertoires, and the extent to which these are shared between individuals...
February 13, 2019: Nature
https://read.qxmd.com/read/30755308/ushering-in-integrated-t-cell-repertoire-profiling-in-cancer
#8
REVIEW
Ning Jiang, Alexandra A Schonnesen, Ke-Yue Ma
Advances in immune profiling techniques have dramatically changed the cancer immunotherapy and monitoring landscape. High-throughput protein and gene expression technologies have paved the way for the discovery of therapeutic targets and biomarkers, and have made monitoring therapeutic response possible through the ability to independently assay the phenotype, specificity, exhaustion status, and lineage of single T cells. Although valuable insights into response profiling have been gained with current technologies, it has become evident that single-method profiling is insufficient to accurately capture an antitumor T cell response...
February 2019: Trends in Cancer
https://read.qxmd.com/read/30747723/longitudinally-persistent-cerebrospinal-fluid-b-cells-can-resist-treatment-in-multiple-sclerosis
#9
Ariele L Greenfield, Ravi Dandekar, Akshaya Ramesh, Erica L Eggers, Hao Wu, Sarah Laurent, William Harkin, Natalie S Pierson, Martin S Weber, Roland G Henry, Antje Bischof, Bruce Ac Cree, Stephen L Hauser, Michael R Wilson, H-Christian von Büdingen
B-cells are key contributors to chronic autoimmune pathology in multiple sclerosis (MS). Clonally related B-cells exist in the cerebrospinal fluid (CSF), meninges, and central nervous system (CNS) parenchyma of MS patients. We sought to investigate the presence of clonally related B-cells over time by performing immunoglobulin heavy chain variable region repertoire sequencing on B-cells from longitudinally collected blood and CSF samples of MS patients (n=10). All patients were untreated at the time of the initial sampling; the majority (n=7) were treated with immune modulating therapies 1...
February 12, 2019: JCI Insight
https://read.qxmd.com/read/30742662/mirna-expression-profiles-and-molecular-networks-in-resting-and-lps-activated-bv-2-microglia-effect-of-cannabinoids
#10
Ana Juknat, Fuying Gao, Giovanni Coppola, Zvi Vogel, Ewa Kozela
Mammalian microRNAs (miRNAs) play a critical role in modulating the response of immune cells to stimuli. Cannabinoids are known to exert beneficial actions such as neuroprotection and immunosuppressive activities. However, the underlying mechanisms which contribute to these effects are not fully understood. We previously reported that the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD) differ in their anti-inflammatory signaling pathways. Using lipopolysaccharide (LPS) to stimulate BV-2 microglial cells, we examined the role of cannabinoids on the expression of miRNAs...
2019: PloS One
https://read.qxmd.com/read/30742125/an-injectable-bone-marrow-like-scaffold-enhances-t-cell-immunity-after-hematopoietic-stem-cell-transplantation
#11
Nisarg J Shah, Angelo S Mao, Ting-Yu Shih, Matthew D Kerr, Azeem Sharda, Theresa M Raimondo, James C Weaver, Vladimir D Vrbanac, Maud Deruaz, Andrew M Tager, David J Mooney, David T Scadden
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for multiple disorders, but deficiency and dysregulation of T cells limit its utility. Here we report a biomaterial-based scaffold that mimics features of T cell lymphopoiesis in the bone marrow. The bone marrow cryogel (BMC) releases bone morphogenetic protein-2 to recruit stromal cells and presents the Notch ligand Delta-like ligand-4 to facilitate T cell lineage specification of mouse and human hematopoietic progenitor cells...
February 11, 2019: Nature Biotechnology
https://read.qxmd.com/read/30742113/landscape-of-b-cell-immunity-and-related-immune-evasion-in-human-cancers
#12
Xihao Hu, Jian Zhang, Jin Wang, Jingxin Fu, Taiwen Li, Xiaoqi Zheng, Binbin Wang, Shengqing Gu, Peng Jiang, Jingyu Fan, Xiaomin Ying, Jing Zhang, Michael C Carroll, Kai W Wucherpfennig, Nir Hacohen, Fan Zhang, Peng Zhang, Jun S Liu, Bo Li, X Shirley Liu
Tumor-infiltrating B cells are an important component in the microenvironment but have unclear anti-tumor effects. We enhanced our previous computational algorithm TRUST to extract the B cell immunoglobulin hypervariable regions from bulk tumor RNA-sequencing data. TRUST assembled more than 30 million complementarity-determining region 3 sequences of the B cell heavy chain (IgH) from The Cancer Genome Atlas. Widespread B cell clonal expansions and immunoglobulin subclass switch events were observed in diverse human cancers...
February 11, 2019: Nature Genetics
https://read.qxmd.com/read/30737147/the-histone-methyltransferase-setdb1-controls-t-helper-cell-lineage-integrity-by-repressing-endogenous-retroviruses
#13
Véronique Adoue, Bénédicte Binet, Agathe Malbec, Joanna Fourquet, Paola Romagnoli, Joost P M van Meerwijk, Sebastian Amigorena, Olivier P Joffre
Upon activation, naive CD4+ T cells differentiate into distinct T cell subsets via processes reliant on epigenetically regulated, lineage-specific developmental programs. Here, we examined the function of the histone methyltransferase SETDB1 in T helper (Th) cell differentiation. Setdb1-/- naive CD4+ T cells exhibited exacerbated Th1 priming, and when exposed to a Th1-instructive signal, Setdb1-/- Th2 cells crossed lineage boundaries and acquired a Th1 phenotype. SETDB1 did not directly control Th1 gene promoter activity but relied instead on deposition of the repressive H3K9me3 mark at a restricted and cell-type-specific set of endogenous retroviruses (ERVs) located in the vicinity of genes involved in immune processes...
January 31, 2019: Immunity
https://read.qxmd.com/read/30737146/clonal-deletion-of-tumor-specific-t-cells-by-interferon-%C3%AE-confers-therapeutic-resistance-to-combination-immune-checkpoint-blockade
#14
Chien-Chun Steven Pai, John T Huang, Xiaoqing Lu, Donald M Simons, Chanhyuk Park, Anthony Chang, Whitney Tamaki, Eric Liu, Kole T Roybal, Jane Seagal, Mingyi Chen, Katsunobu Hagihara, Xiao X Wei, Michel DuPage, Serena S Kwek, David Y Oh, Adil Daud, Katy K Tsai, Clint Wu, Li Zhang, Marcella Fasso, Ravi Sachidanandam, Anitha Jayaprakash, Ingrid Lin, Amy-Jo Casbon, Gillian A Kinsbury, Lawrence Fong
Resistance to checkpoint-blockade treatments is a challenge in the clinic. We found that although treatment with combined anti-CTLA-4 and anti-PD-1 improved control of established tumors, this combination compromised anti-tumor immunity in the low tumor burden (LTB) state in pre-clinical models as well as in melanoma patients. Activated tumor-specific T cells expressed higher amounts of interferon-γ (IFN-γ) receptor and were more susceptible to apoptosis than naive T cells. Combination treatment induced deletion of tumor-specific T cells and altered the T cell repertoire landscape, skewing the distribution of T cells toward lower-frequency clonotypes...
February 1, 2019: Immunity
https://read.qxmd.com/read/30735729/immune-aging-in-diabetes-and-its-implications-in-wound-healing
#15
REVIEW
J Moura, P Madureira, E C Leal, A C Fonseca, E Carvalho
Immune systems have evolved to recognize and eliminate pathogens and damaged cells. In humans, it is estimated to recognize 109 epitopes and natural selection ensures that clonally expanded cells replace unstimulated cells and overall immune cell numbers remain stationary. But, with age, it faces continuous repertoire restriction and concomitant accumulation of primed cells. Changes shaping the aging immune system have bitter consequences because, as inflammatory responses gain intensity and duration, tissue-damaging immunity and inflammatory disease arise...
February 5, 2019: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://read.qxmd.com/read/30733445/mosaic-deletion-patterns-of-the-human-antibody-heavy-chain-gene-locus-shown-by-bayesian-haplotyping
#16
Moriah Gidoni, Omri Snir, Ayelet Peres, Pazit Polak, Ida Lindeman, Ivana Mikocziova, Vikas Kumar Sarna, Knut E A Lundin, Christopher Clouser, Francois Vigneault, Andrew M Collins, Ludvig M Sollid, Gur Yaari
Analysis of antibody repertoires by high-throughput sequencing is of major importance in understanding adaptive immune responses. Our knowledge of variations in the genomic loci encoding immunoglobulin genes is incomplete, resulting in conflicting VDJ gene assignments and biased genotype and haplotype inference. Haplotypes can be inferred using IGHJ6 heterozygosity, observed in one third of the people. Here, we propose a robust novel method for determining VDJ haplotypes by adapting a Bayesian framework. Our method extends haplotype inference to IGHD- and IGHV-based analysis, enabling inference of deletions and copy number variations in the entire population...
February 7, 2019: Nature Communications
https://read.qxmd.com/read/30723589/neoantigen-characteristics-in-the-context-of-the-complete-predicted-mhc-class-i-self-immunopeptidome
#17
Scott D Brown, Robert A Holt
The self-immunopeptidome is the repertoire of all self-peptides that can be presented by the combination of MHC variants carried by an individual, defined by their HLA genotype. Each MHC variant presents a distinct set of self-peptides, and the number of peptides in a set is variable. Subjects carrying MHC variants that present fewer self-peptides should also present fewer mutated peptides, resulting in decreased immune pressure on tumor cells. To explore this, we predicted peptide-MHC binding values using all unique 8-11mer human peptides in the human proteome and all available HLA class I allelic variants, for a total of 134 billion unique peptide--MHC binding predictions...
2019: Oncoimmunology
https://read.qxmd.com/read/30723470/the-immune-system-computes-the-state-of-the-body-crowd-wisdom-machine-learning-and-immune-cell-reference-repertoires-help-manage-inflammation
#18
Irun R Cohen, Sol Efroni
Here, we outline an overview of the mammalian immune system that updates and extends the classical clonal selection paradigm. Rather than focusing on strict self-not-self discrimination, we propose that the system orchestrates variable inflammatory responses that maintain the body and its symbiosis with the microbiome while eliminating the threat from pathogenic infectious agents and from tumors. The paper makes four points: The immune system classifies healthy and pathologic states of the body-including both self and foreign elements-by deploying individual lymphocytes as cellular computing machines; immune cells transform input signals from the body into an output of specific immune reactions...
2019: Frontiers in Immunology
https://read.qxmd.com/read/30721553/tcr%C3%AE-repertoire-of-memory-t-cell-reveals-potential-role-for-e-coli-in-the-pathogenesis-of-primary-biliary-cholangitis
#19
Xianliang Hou, Yida Yang, Jianing Chen, Hongyu Jia, Ping Zeng, Longxian Lv, Yingfeng Lu, Xiangdong Liu, Hongyan Diao
BACKGROUND: Primary biliary cholangitis (PBC) is an organ-specific, T cell mediated autoimmune disease which is characterized by the breakdown of self-tolerance to the highly conserved pyruvate dehydrogenase complex, especially the pyruvate dehydrogenase E2 complex (PDC-E2). However, the molecular mechanism of breakdown of self-tolerance is still unclear. METHODS: A combination of multiplex-PCR and immune repertoire sequencing (IR-seq) was used for a standardized analysis of memory T cell receptor (TCR) β-chain repertoire of PBC patient and healthy volunteers...
February 5, 2019: Liver International: Official Journal of the International Association for the Study of the Liver
https://read.qxmd.com/read/30718829/breaking-the-law-unconventional-strategies-for-antibody-diversification
#20
REVIEW
Alexia Kanyavuz, Annaelle Marey-Jarossay, Sébastien Lacroix-Desmazes, Jordan D Dimitrov
Antibodies are essential components of adaptive immunity. A typical antibody repertoire comprises an enormous diversity of antigen-binding specificities, which are generated by the genetic processes of recombination and mutation. Accumulating evidence suggests that the immune system can exploit additional strategies to diversify the repertoire of antigen specificities. These unconventional mechanisms exclusively target the antigen-binding sites of immunoglobulins and include the insertion of large amino acid sequences, post-translational modifications, conformational heterogeneity and use of nonprotein cofactor molecules...
February 4, 2019: Nature Reviews. Immunology
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