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Immune Repertoire

Jason Anthony Vander Heiden, Susanna Marquez, Nishanth Marthandan, Syed Ahmad Chan Bukhari, Christian E Busse, Brian Corrie, Uri Hershberg, Steven H Kleinstein, Frederick A Matsen Iv, Duncan K Ralph, Aaron M Rosenfeld, Chaim A Schramm, Scott Christley, Uri Laserson
Increased interest in the immune system's involvement in pathophysiological phenomena coupled with decreased DNA sequencing costs have led to an explosion of antibody and T cell receptor sequencing data collectively termed "adaptive immune receptor repertoire sequencing" (AIRR-seq or Rep-Seq). The AIRR Community has been actively working to standardize protocols, metadata, formats, APIs, and other guidelines to promote open and reproducible studies of the immune repertoire. In this paper, we describe the work of the AIRR Community's Data Representation Working Group to develop standardized data representations for storing and sharing annotated antibody and T cell receptor data...
2018: Frontiers in Immunology
Thitiya Sae-Jung, Panjana Sengprasert, Jirun Apinun, Srihatach Ngarmukos, Pongsak Yuktanandana, Aree Tanavalee, Rangsima Reantragoon
OBJECTIVE: Osteoarthritis (OA) is a condition that features inflammation and immune responses of innate and adaptive immunity. The role of T cells in knee OA pathogenesis is still unclear. Our aim was to characterize T cell functions and their clonality in patients with knee OA in peripheral blood (PB) and infrapatellar fat pads (IPFP). METHODS: We isolated T cells from PB and IPFP of patients with knee OA and PB of healthy individuals and determined soluble mediators produced from these cells...
October 15, 2018: Journal of Rheumatology
Longlong Wang, Wei Zhang, Liya Lin, Xiao Li, Nitin K Saksena, Jinghua Wu, Shiyu Wang, Joseph G Joyce, Xiuqing Zhang, Huanming Yang, Jian Wang, I-Ming Wang, Xiao Liu
The exploitation of various human immunodeficiency virus type-1 (HIV-1) vaccines has posed great challenges for the researchers in precisely evaluating the vaccine-induced immune responses, however, the understanding of vaccination response suffers from the lack of unbiased characterization of the immune landscape. The rapid development of high throughput sequencing (HTS) makes it possible to scrutinize the extremely complicated immunological responses during vaccination. In the current study, three vaccines, namely N36, N51, and 5-Helix based on the HIV-1 gp41 pre-hairpin fusion intermediate were applied in rhesus macaques...
2018: Frontiers in Immunology
Robert Craig Findly, Frank D Niagro, Ryan P Sweeney, Alvin C Camus, Harry W Dickerson
Rearranged V(D)J genes coding for T cell receptor α and β chains are integrated into the germline genome of channel catfish. Previous analysis of expressed TCR Vβ2 repertoires demonstrated that channel catfish express multiple public clonotypes, which were shared among all the fish, following infection with a common protozoan parasite. In each case a single DNA sequence was predominately used to code for a public clonotype. We show here that the rearranged VDJ genes coding for these expressed public Vβ2 clonotypes can be amplified by PCR from germline DNA isolated from oocytes and erythrocytes...
2018: Frontiers in Immunology
Afsar R Naqvi, Jennifer Shango, Alexandra Seal, Deepak Shukla, Salvador Nares
The oral cavity incessantly encounters a plethora of microorganisms. Effective and efficient oral innate and adaptive immune responses are incumbent to maintain healthy mucosa. A higher prevalence of Human Herpesviruses (HHV), a family of large enveloped DNA viruses, has been reported in multiple oral inflammatory diseases suggesting their involvement in disease progression. However, the viral components contributing to oral disease remain obscure. MicroRNAs (miRNA) are non-protein coding, single stranded ribonucleic acid (RNA) molecules that post-transcriptionally regulate diverse messenger RNAs...
2018: Frontiers in Immunology
Zsuzsanna Szepesi, Oscar Manouchehrian, Sara Bachiller, Tomas Deierborg
Microglia are ramified cells that exhibit highly motile processes, which continuously survey the brain parenchyma and react to any insult to the CNS homeostasis. Although microglia have long been recognized as a crucial player in generating and maintaining inflammatory responses in the CNS, now it has become clear, that their function are much more diverse, particularly in the healthy brain. The innate immune response and phagocytosis represent only a little segment of microglia functional repertoire that also includes maintenance of biochemical homeostasis, neuronal circuit maturation during development and experience-dependent remodeling of neuronal circuits in the adult brain...
2018: Frontiers in Cellular Neuroscience
Edoardo Elia, Fabrizio Montecucco, Piero Portincasa, Amirhossein Sahebkar, Hamid Mollazadeh, Federico Carbone
Although coronary thrombosis (CT) is integral to cardiovascular outcomes, the underlying pathophysiological mechanisms remain unclear. CT may occur in case of atherosclerotic plaque erosion/rupture, or even after stenting implantation. Platelets (PLT) activation is the keystone of atherothrombosis and depends on many dysregulated elements, including endothelial dysfunction, oxidized lipoproteins, and immune response. Besides the classical view of PLT as an effector of hemostatic response, a new repertoire of PLT activities is emerging...
October 14, 2018: Journal of Cellular Physiology
Pouya Faridi, Chen Li, Sri H Ramarathinam, Julian P Vivian, Patricia T Illing, Nicole A Mifsud, Rochelle Ayala, Jiangning Song, Linden J Gearing, Paul J Hertzog, Nicola Ternette, Jamie Rossjohn, Nathan P Croft, Anthony W Purcell
The diversity of peptides displayed by class I human leukocyte antigen (HLA) plays an essential role in T cell immunity. The peptide repertoire is extended by various posttranslational modifications, including proteasomal splicing of peptide fragments from distinct regions of an antigen to form nongenomically templated cis-spliced sequences. Previously, it has been suggested that a fraction of the immunopeptidome constitutes such cis-spliced peptides; however, because of computational limitations, it has not been possible to assess whether trans-spliced peptides (i...
October 12, 2018: Science Immunology
Nicholas C Wu, Seiya Yamayoshi, Mutsumi Ito, Ryuta Uraki, Yoshihiro Kawaoka, Ian A Wilson
Discovery and characterization of broadly neutralizing antibodies (bnAbs) to the influenza hemagglutinin (HA) stem have provided insights for the development of a universal flu vaccine. Identification of signature features common to bnAbs from different individuals will be key to guiding immunogen design. S9-3-37 is a bnAb isolated from a healthy H5N1 vaccinee. Here, structural characterization reveals that the D3-9 gene segment of S9-3-37 contributes most of the interaction surface with the highly conserved stem epitope on HA...
October 10, 2018: Cell Host & Microbe
Neal Van Hoeven, Steven Wiley, Emily Gage, Andrew Fiore-Gartland, Brian Granger, Sean Gray, Christopher Fox, David E Clements, D Elliot Parks, Scott Winram, Dan T Stinchcomb, Steven G Reed, Rhea N Coler
Members of the Flaviviridae family are the leading causes of mosquito-borne viral disease worldwide. While dengue virus is the most prevalent, the recent Zika virus outbreak in the Americas triggered a WHO public health emergency, and yellow fever and West Nile viruses (WNV) continue to cause regional epidemics. Given the sporadic nature of flaviviral epidemics both temporally and geographically, there is an urgent need for vaccines that can rapidly provide effective immunity. Protection from flaviviral infection is correlated with antibodies to the viral envelope (E) protein, which encodes receptor binding and fusion functions...
2018: NPJ Vaccines
Siddhartha Sharma, Louis Gioia, Brian Abe, Marie Holt, Anne Costanzo, Lisa Kain, Andrew Su, Luc Teyton
The difficulty of studying small tissue samples and rare cell populations have been some of the main limitations in performing efficient translational studies of immune mediated diseases. Many of these conditions are grouped under the name of a single disease whilst there are strong suggestions that disease heterogeneity leads to variable disease progression as well as therapeutic responses. The recent development of single cell techniques, such as single cell RNA sequencing, gene expression profiling, or multiparametric cytometry, is likely to be a turning point...
October 6, 2018: Molecular Immunology
Slavica Vuckovic, Simone A Minnie, David Smith, Kate H Gartlan, Thomas S Watkins, Kate A Markey, Pamela Mukhopadhyay, Camille Guillerey, Rachel D Kuns, Kelly R Locke, Antonia L Pritchard, Peter A Johansson, Antiopi Varelias, Ping Zhang, Nicholas D Huntington, Nicola Waddell, Marta Chesi, John J Miles, Mark J Smyth, Geoffrey R Hill
Transplantation with autologous hematopoietic progenitors remains an important consolidation treatment for multiple myeloma (MM) patients and is thought to prolong disease plateau-phase by providing intensive cytoreduction. However, transplantation induces inflammation in the context of profound lymphodepletion that may cause hitherto unexpected immunological effects. We developed preclinical models of bone marrow transplantation (BMT) for MM using Vk*MYC myeloma-bearing recipients and donors that were myeloma-naïve or were myeloma-experienced to simulate autologous transplantation...
October 9, 2018: Journal of Clinical Investigation
Aaron M Rosenfeld, Wenzhao Meng, Eline T Luning Prak, Uri Hershberg
ImmuneDB is a system for storing and analyzing high-throughput immune receptor sequencing data. Unlike most existing tools, which utilize flat-files, ImmuneDB stores data in a well-structured MySQL database, enabling efficient data queries. It can take raw sequencing data as input and annotate receptor gene usage, infer clonotypes, aggregate results, and run common downstream analyses such as calculating selection pressure and constructing clonal lineages. Alternatively, pre-annotated data can be imported and analyzed data can be exported in a variety of common Adaptive Immune Receptor Repertoire (AIRR) file formats...
2018: Frontiers in Immunology
Agathe Jouet, Diane G O Saunders, Mark McMullan, Ben Ward, Oliver Furzer, Florian Jupe, Volkan Cevik, Ingo Hein, Gaetan J A Thilliez, Eric Holub, Cock van Oosterhout, Jonathan D G Jones
Physiological races of the oomycete Albugo candida are biotrophic pathogens of diverse plant species, primarily the Brassicaceae, and cause infections that suppress host immunity to other pathogens. However, A. candida race diversity and the consequences of host immunosuppression are poorly understood in the field. We report a method that enables sequencing of DNA of plant pathogens and plant-associated microbes directly from field samples (Pathogen Enrichment Sequencing: PenSeq). We apply this method to explore race diversity in A...
October 5, 2018: New Phytologist
Marit M Melssen, Walter Olson, Nolan A Wages, Brian J Capaldo, Ileana S Mauldin, Adela Mahmutovic, Ciara Hutchison, Cornelis J M Melief, Timothy N Bullock, Victor H Engelhard, Craig L Slingluff
Integrins α1β1 (CD49a), α2β1 (CD49b) and αEβ7 (CD103) mediate retention of lymphocytes in peripheral tissues, and their expression is upregulated on tumor infiltrating lymphocytes (TIL) compared to circulating lymphocytes. Little is known about what induces expression of these retention integrins (RI) nor whether RI define subsets in the tumor microenvironment (TME) with a specific phenotype. Human metastatic melanoma-derived CD8 TIL could be grouped into five subpopulations based on RI expression patterns: RIneg , CD49a+ only, CD49a+ CD49b+ , CD49a+ CD103+ , or positive for all three RI...
2018: Oncoimmunology
Hung Cao Dinh, Rose Njemini, Oscar Okwudiri Onyema, Ingo Beyer, Keliane Liberman, Liza De Dobbeleer, Wim Renmans, Sam Vander Meeren, Kristin Jochmans, Andreas Delaere, Veerle Knoop, Ivan Bautmans
Ageing is characterized by a progressive decline in immune function known as immunosenescence (IS). While the causes of IS are likely to be multi-factorial, an age-associated accumulation of senescent T-cells and decreased naïve T-cell repertoire are key contributors to the phenomenon. On the other hand, there is a growing consensus that physical exercise may improve immune response in ageing. However, the optimum training modality required to obtain beneficial adaptations in older subjects is lacking. Therefore, we aimed to investigate the effects of exercise modality on T-cell phenotypes in older women...
October 4, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Elín I Magnúsdóttir, Mirjana Grujic, Axel Roers, Karin Hartmann, Gunnar Pejler, Malin C Lagerström
Subcutaneous formalin injections are used as a model for tissue injury-induced pain where formalin induces pain and inflammation indirectly by crosslinking proteins, and directly through activation of the transient receptor potential A1 receptor on primary afferents. Activation of primary afferents leads to both central and peripheral release of neurotransmitters. Mast cells are found in close proximity to peripheral sensory nerve endings and express receptors for neurotransmitters released by the primary afferents, contributing to the neuro/immune interface...
October 3, 2018: Molecular Pain
Siddharth Krishnan, Ian E Prise, Kelly Wemyss, Louis P Schenck, Hayley M Bridgeman, Flora A McClure, Tamsin Zangerle-Murray, Conor O'Boyle, Thomas A Barbera, Faiza Mahmood, Dawn M E Bowdish, Dietmar M W Zaiss, John R Grainger, Joanne E Konkel
γδ T cells are enriched at barrier sites such as the gut, skin, and lung, where their roles in maintaining barrier integrity are well established. However, how these cells contribute to homeostasis at the gingiva, a key oral barrier and site of the common chronic inflammatory disease periodontitis, has not been explored. Here we demonstrate that the gingiva is policed by γδ T cells with a T cell receptor (TCR) repertoire that diversifies during development. Gingival γδ T cells accumulated rapidly after birth in response to barrier damage, and strikingly, their absence resulted in enhanced pathology in murine models of the oral inflammatory disease periodontitis...
October 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
Kara C Hoover
Humans have a comparatively higher rate of more polymorphisms in regulatory regions of the primate CCR5 gene, an immune system gene with both general and specific functions. This has been interpreted as allowing flexibility and diversity of gene expression in response to varying disease loads. A broad expression repertoire is useful to humans-the only globally distributed primate-due to our unique adaptive pattern that increased pathogen exposure and disease loads (e.g., sedentism, subsistence practices). The main objective of the study was to determine if the previously observed human pattern of increased variation extended to other members of our genus, Homo...
2018: PloS One
Simar Pal Singh, Marjolein J W de Bruijn, Mariana P de Almeida, Ruud W J Meijers, Lars Nitschke, Anton W Langerak, Saravanan Y Pillai, Ralph Stadhouders, Rudi W Hendriks
Chronic lymphocytic leukemia (CLL) can be divided into prognostically distinct subsets with stereotyped or non-stereotyped, mutated or unmutated B cell receptors (BCRs). Individual subsets vary in antigen specificity and origin, but the impact of antigenic pressure on the CLL BCR repertoire remains unknown. Here, we employed IgH.TE μ mice that spontaneously develop CLL, expressing mostly unmutated BCRs of which ~35% harbor VH 11-2/Vκ14-126 and recognize phosphatidylcholine. Proportions of VH 11/Vκ14-expressing CLL were increased in the absence of functional germinal centers in IgH...
2018: Frontiers in Immunology
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