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Immune Repertoire

Swapnil Mahajan, Randi Vita, Deborah Shackelford, Jerome Lane, Veronique Schulten, Laura Zarebski, Martin Closter Jespersen, Paolo Marcatili, Morten Nielsen, Alessandro Sette, Bjoern Peters
The Immune Epitope Database (IEDB) is a free public resource which catalogs experiments characterizing immune epitopes. To accommodate data from next generation repertoire sequencing experiments, we recently updated how we capture and query epitope specific antibodies and T cell receptors. Specifically, we are now storing partial receptor sequences sufficient to determine CDRs and VDJ gene usage which are commonly identified by repertoire sequencing. For previously captured full length receptor sequencing data, we have calculated the corresponding CDR sequences and gene usage information using IMGT numbering and VDJ gene nomenclature format...
2018: Frontiers in Immunology
Soizic Garaud, Pawel Zayakin, Laurence Buisseret, Undine Rulle, Karina Silina, Alexandre de Wind, Gert Van den Eyden, Denis Larsimont, Karen Willard-Gallo, Aija Linē
An important role for tumor infiltrating B lymphocytes (TIL-B) in the immune response to cancer is emerging; however, very little is known about the antigen specificity of antibodies produced in situ . The presence of IgA antibodies in the tumor microenvironment has been noted although their biological functions and clinical significance are unknown. This study used a 91-antigen microarray to examine the IgG and IgA autoantibody repertoires in breast cancer (BC). Tumor and adjacent breast tissue supernatants and plasma from BC patients together with normal breast tissue supernatants and plasma from healthy controls (patients undergoing mammary reduction and healthy blood donors) were analyzed to investigate relationships between autoantibodies and the clinical, histological and immunological features of tumors...
2018: Frontiers in Immunology
Roberto Ferrara, Sandrine Susini, Aurélien Marabelle
The potential role of anti-CTLA-4 antibodies in depleting intratumoral T-regulatory cells (iTregs) is still a matter of debate. In fact, if on one hand a recent study showed that ipilimumab and tremelimumab do not reduce Tregs in bladder, prostate and melanoma human cancers, on the other hand several other reports described opposite results. Basically, the depletion of iTregs may concern only CTLA-4+ iTregs and the evaluation of this population by immunohistochemistry may be challenging because CTLA-4 is highly express in the cytoplasm rather than on the membrane of these cells...
December 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Wouter Scheper, Sander Kelderman, Lorenzo F Fanchi, Carsten Linnemann, Gavin Bendle, Marije A J de Rooij, Christian Hirt, Riccardo Mezzadra, Maarten Slagter, Krijn Dijkstra, Roelof J C Kluin, Petur Snaebjornsson, Katy Milne, Brad H Nelson, Henry Zijlmans, Gemma Kenter, Emile E Voest, John B A G Haanen, Ton N Schumacher
Infiltration of human cancers by T cells is generally interpreted as a sign of immune recognition, and there is a growing effort to reactivate dysfunctional T cells at such tumor sites1 . However, these efforts only have value if the intratumoral T cell receptor (TCR) repertoire of such cells is intrinsically tumor reactive, and this has not been established in an unbiased manner for most human cancers. To address this issue, we analyzed the intrinsic tumor reactivity of the intratumoral TCR repertoire of CD8+ T cells in ovarian and colorectal cancer-two tumor types for which T cell infiltrates form a positive prognostic marker2,3 ...
December 3, 2018: Nature Medicine
Lucy A Eddowes, Kinda Al-Hourani, Narayan Ramamurthy, Jamie Frankish, Hannah T Baddock, Cynthia Sandor, John D Ryan, Dahlene N Fusco, João Arezes, Eleni Giannoulatou, Sara Boninsegna, Stephane Chevaliez, Benjamin M J Owens, Chia Chi Sun, Paolo Fabris, Maria Teresa Giordani, Diego Martines, Slobodan Vukicevic, John Crowe, Herbert Y Lin, Jan Rehwinkel, Peter J McHugh, Marco Binder, Jodie L Babitt, Raymond T Chung, Matthew W Lawless, Andrew E Armitage, Caleb Webber, Paul Klenerman, Hal Drakesmith
Understanding the control of viral infections is of broad importance. Chronic hepatitis C virus (HCV) infection causes decreased expression of the iron hormone hepcidin, which is regulated by hepatic bone morphogenetic protein (BMP)/SMAD signalling. We found that HCV infection and the BMP/SMAD pathway are mutually antagonistic. HCV blunted induction of hepcidin expression by BMP6, probably via tumour necrosis factor (TNF)-mediated downregulation of the BMP co-receptor haemojuvelin. In HCV-infected patients, disruption of the BMP6/hepcidin axis and genetic variation associated with the BMP/SMAD pathway predicted the outcome of infection, suggesting that BMP/SMAD activity influences antiviral immunity...
December 3, 2018: Nature Microbiology
Evan W McConnell, Philip Berg, Timothy J Westlake, Katherine M Wilson, George V Popescu, Leslie M Hicks, Sorina C Popescu
A surge in the accumulation of oxidants generates shifts in the cellular redox potential during early stages of plant infection with pathogens and activation of effector-triggered immunity (ETI). The redoxome, defined as the proteome-wide oxidative modifications of proteins caused by oxidants, has a well-known impact on stress responses in metazoans. However, the identity of proteins and the residues sensitive to oxidation during the plant immune response remain largely unknown. Previous studies of the thimet oligopeptidases TOP1 and TOP2 placed them in the SA-dependent branch of ETI, with a current model wherein TOPs sustain interconnected organellar and cytosolic pathways that modulate the oxidative burst and development of cell death...
December 3, 2018: Plant Physiology
Manuel Rojas, Paula Restrepo-Jiménez, Diana M Monsalve, Yovana Pacheco, Yeny Acosta-Ampudia, Carolina Ramírez-Santana, Patrick S C Leung, Aftab A Ansari, M Eric Gershwin, Juan-Manuel Anaya
Molecular mimicry is one of the leading mechanisms by which infectious or chemical agents may induce autoimmunity. It occurs when similarities between foreign and self-peptides favor an activation of autoreactive T or B cells by a foreign-derived antigen in a susceptible individual. However, molecular mimicry is unlikely to be the only underlying mechanism for autoimmune responses; other factors such as breach in central tolerance, non-specific bystander activation, or persistent antigenic stimuli (amongst others) may also contribute to the development of autoimmune diseases...
December 2018: Journal of Autoimmunity
Ramesh Chandra Halder, Cynthia Tran, Priti Prasad, Jing Wang, Dhiraj Nallapothula, Tatsuya Ishikawa, Meiying Wang, Dirk M Zajonc, Ram Raj Singh
Glycosphingolipids and glycerophospholipids bind CD1d. Glycosphingolipid-reactive invariant NKT-cells (iNKT) exhibit myriad immune effects, however, little is known about the functions of phospholipid-reactive T-cells (PLT). We report that the normal mouse immune repertoire contains αβ T-cells, which recognize self-glycerophospholipids such as phosphatidic acid (PA) in a CD1d-restricted manner and don't cross-react with iNKT-cell ligands. PA bound to CD1d in the absence of lipid transfer proteins. Upon in vivo priming, PA induced an expansion and activation of T-cells in Ag-specific manner...
December 3, 2018: European Journal of Immunology
Kelen Cristina Ribeiro Malmegrim, João Rodrigues Lima-Júnior, Lucas Coelho Marlière Arruda, Júlia Teixeira Cottas de Azevedo, Gislane Lelis Vilela de Oliveira, Maria Carolina Oliveira
Phase I/II clinical trials of autologous hematopoietic stem cell transplantation (AHSCT) have led to increased safety and efficacy of this therapy for severe and refractory autoimmune diseases (AD). Recent phase III randomized studies have demonstrated that AHSCT induces long-term disease remission in most patients without any further immunosuppression, with superior efficacy when compared to conventional treatments. Immune monitoring studies have revealed the regeneration of a self-tolerant T and B cell repertoire, enhancement of immune regulatory mechanisms, and changes toward an anti-inflammatory milieu in patients that are responsive to AHSCT...
2018: Frontiers in Immunology
Linda Wampach, Anna Heintz-Buschart, Joëlle V Fritz, Javier Ramiro-Garcia, Janine Habier, Malte Herold, Shaman Narayanasamy, Anne Kaysen, Angela H Hogan, Lutz Bindl, Jean Bottu, Rashi Halder, Conny Sjöqvist, Patrick May, Anders F Andersson, Carine de Beaufort, Paul Wilmes
The rate of caesarean section delivery (CSD) is increasing worldwide. It remains unclear whether disruption of mother-to-neonate transmission of microbiota through CSD occurs and whether it affects human physiology. Here we perform metagenomic analysis of earliest gut microbial community structures and functions. We identify differences in encoded functions between microbiomes of vaginally delivered (VD) and CSD neonates. Several functional pathways are over-represented in VD neonates, including lipopolysaccharide (LPS) biosynthesis...
November 30, 2018: Nature Communications
Geoffrey T Norris, Jonathan Kipnis
Recent advances have directed our knowledge of the immune system from a narrative of "self" versus "nonself" to one in which immune function is critical for homeostasis of organs throughout the body. This is also the case with respect to the central nervous system (CNS). CNS immunity exists in a segregated state, with a marked partition occurring between the brain parenchyma and meningeal spaces. While the brain parenchyma is patrolled by perivascular macrophages and microglia, the meningeal spaces are supplied with a diverse immune repertoire...
November 30, 2018: Journal of Experimental Medicine
Ilham Naili, Juliette Vinot, Barbara C Baudner, Annick Bernalier-Donadille, Mariagrazia Pizza, Mickaël Desvaux, Grégory Jubelin, Ugo D'Oro, Cecilia Buonsanti
Emergence and dissemination of multidrug resistance among pathogenic Escherichia coli have posed a serious threat to public health across developing and developed countries. In combination with a flexible repertoire of virulence mechanisms, E. coli can cause a vast range of intestinal (InPEC) and extraintestinal (ExPEC) diseases but only a very limited number of antibiotics still remains effective against this pathogen. Hence, a broad spectrum E. coli vaccine could be a promising alternative to prevent the burden of such diseases, while offering the potential for covering against several InPEC and ExPEC at once...
November 29, 2018: Vaccine
Mehdi Najar, Emerence Crompot, Gordana Raicevic, Etienne M Sokal, Mustapha Najimi, Laurence Lagneaux
Background: Being non-immunogenic and capable of achieving major metabolic liver functions, adult-derived human liver stem/progenitor cells (ADHLSCs) are of special interest in the field of liver cell therapy. The cytokine repertoire of engrafted cells may have critical impacts on the immune response balance, particularly during cell transplantation. Methods: In this work, we analyzed the cytokinome of ADHLSCs during hepatogenic differentiation (HD) following stimulation with a mixture of inflammatory cytokines (I) in vitro and compared it to that of mature hepatocytes...
October 2018: Hepatobiliary Surgery and Nutrition
Bhakti Patel, Rajanya Banerjee, Madhubanti Basu, Saswati S Lenka, Mahismita Paichha, Mrinal Samanta, Surajit Das
The molecular crosstalk of proximal innate immune receptor signaling mediated by Toll-like receptors (TLRs) is crucial in generating an adaptive immune response. The extracellular-signal regulated kinases (ERK) participate in propagating intracellular signals initiated by stimulated TLRs to transcription factors eliciting cytokine release. Although ERK signaling has been extensively studied in mammalian counterparts, very little is known about its existence in carps and its role in augmentation of immunoglobulin (Ig) synthesis...
November 26, 2018: Molecular Immunology
William Reid Bolus, Arion J Kennedy, Alyssa H Hasty
While many studies have characterized the inflammatory disposition of adipose tissue (AT) during obesity, far fewer have dissected how such inflammation resolves during the process of physiological weight loss. In addition, new immune cells, such as the eosinophil, have been discovered as part of the AT immune cell repertoire. We have therefore characterized how AT eosinophils, associated eosinophilic inflammation, and remodeling processes, fluctuate during a dietary intervention in obese mice. Similar to previous reports, we found that obesity induced by high-fat diet feeding reduced the AT eosinophil content...
November 2018: Physiological Reports
Meriem Attaf, Amna Malik, Mai C Severinsen, Julia Roider, Paul Ogongo, Søren Buus, Thumbi Ndung'u, Alasdair Leslie, Henrik N Kløverpris, Philippa C Matthews, Andrew K Sewell, Philip Goulder
Lack of disease during chronic human cytomegalovirus (CMV) infection depends on the maintenance of a high-frequency CMV-specific T cell response. The composition of the T cell receptor (TCR) repertoire underlying this response remains poorly characterised, especially within African populations in which CMV is endemic from infancy. Here we focus on the immunodominant CD8+ T cell response to the immediate-early 2 (IE-2)-derived epitope NEGVKAAW (NW8) restricted by HLA-B* 44:03, a highly prevalent response in African populations, which in some subjects represents >10% of the circulating CD8+ T cells...
2018: Frontiers in Immunology
Kai Sen Tan, Yan Yan, Wai Ling Hiromi Koh, Liang Li, Hyungwon Choi, Thai Tran, Richard Sugrue, De Yun Wang, Vincent T Chow
In vitro and in vivo research based on cell lines and animals are likely to be insufficient in elucidating authentic biological and physiological phenomena mimicking human systems, especially for generating pre-clinical data on targets and biomarkers. There is an obvious need for a model that can further bridge the gap in translating pre-clinical findings into clinical applications. We have previously generated a model of in vitro differentiated human nasal epithelial cells (hNECs) which elucidated the nasal-initiated repertoire of immune responses against respiratory viruses such as influenza A virus and rhinovirus...
2018: Frontiers in Microbiology
Hillary Koch, Dmytro Starenki, Sara J Cooper, Richard M Myers, Qunhua Li
Sequencing of the T cell receptor repertoire is a powerful tool for deeper study of immune response, but the unique structure of this type of data makes its meaningful quantification challenging. We introduce a new method, the Gamma-GPD spliced threshold model, to address this difficulty. This biologically interpretable model captures the distribution of the TCR repertoire, demonstrates stability across varying sequencing depths, and permits comparative analysis across any number of sampled individuals. We apply our method to several datasets and obtain insights regarding the differentiating features in the T cell receptor repertoire among sampled individuals across conditions...
November 28, 2018: PLoS Computational Biology
Aliki Xochelli, Vasilis Bikos, Eleftheria Polychronidou, Chrysi Galigalidou, Andreas Agathangelidis, Frédéric Charlotte, Panagiotis Moschonas, Zadie Davis, Monica Colombo, Maria Roumelioti, Lesley-Ann Sutton, Patricia Groenen, Michiel van den Brand, Myriam Boudjoghra, Patricia Algara, Alexandra Traverse-Glehen, Ana Ferrer, Evangelia Stalika, Maria Karypidou, George Kanellis, Christina Kalpadakis, Manuella Mollejo, Gerasimos Pangalis, Panayiotis Vlamos, Rose-Marie Amini, Sarka Pospisilova, David Gonzalez, Maurilio Ponzoni, Achilles Anagnostopoulos, Véronique Giudicelli, Marie-Paule Lefranc, Blanca Espinet, Panagiotis Panagiotidis, Miguel Angel Piris, Ming-Qing Du, Richard Rosenquist, Theodora Papadaki, Chrysoula Belessi, Manlio Ferrarini, David Oscier, Dimitrios Tzovaras, Paolo Ghia, Frederic Davi, Anastasia Hadzidimitriou, Kostas Stamatopoulos
The B cell receptor immunoglobulin (BcR IG) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n=488) i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL) as well as provisional entities (n=76) according to the World Health Organization classification. The most striking IG gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different IG gene distributions depending on the primary site of involvement...
November 28, 2018: Journal of Pathology
Natalie J Miller, Candice D Church, Steven P Fling, Rima Kulikauskas, Nirasha Ramchurren, Michi M Shinohara, Harriet M Kluger, Shailender Bhatia, Lisa Lundgren, Martin A Cheever, Suzanne L Topalian, Paul Nghiem
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer that frequently responds to anti-PD-1 therapy. MCC is associated with sun exposure and, in 80% of cases, Merkel cell polyomavirus (MCPyV). MCPyV-specific T and B cell responses provide a unique opportunity to study cancer-specific immunity throughout PD-1 blockade therapy. METHODS: Immune responses were assessed in patients (n = 26) with advanced MCC receiving pembrolizumab. Peripheral blood mononuclear cells (PBMC) were collected at baseline and throughout treatment...
November 27, 2018: Journal for Immunotherapy of Cancer
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