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Immune Repertoire

N Giovannone, J Liang, A Antonopoulos, J Geddes Sweeney, S L King, S M Pochebit, N Bhattacharyya, G S Lee, A Dell, H R Widlund, S M Haslam, C J Dimitroff
Leukocytes are coated with a layer of heterogeneous carbohydrates (glycans) that modulate immune function, in part by governing specific interactions with glycan-binding proteins (lectins). Although nearly all membrane proteins bear glycans, the identity and function of most of these sugars on leukocytes remain unexplored. Here, we characterize the N-glycan repertoire (N-glycome) of human tonsillar B cells. We observe that naive and memory B cells express an N-glycan repertoire conferring strong binding to the immunoregulatory lectin galectin-9 (Gal-9)...
August 17, 2018: Nature Communications
Xin Gao, David F McDermott
Renal cell carcinoma (RCC) is characterized by aberrant angiogenic signaling and an immunogenic tumor microenvironment. Systemic therapies targeting vascular endothelial growth factor and the immune checkpoints programmed cell death protein 1/programmed cell death protein 1 ligand and cytotoxic T-lymphocyte-associated protein 4 have advanced to the forefront of the treatment repertoire against advanced or metastatic RCC (mRCC). In preclinical models, inhibition of vascular endothelial growth factor signaling promotes antitumor immunity and may enhance the efficacy of immune checkpoint blockade...
July 2018: Cancer Journal
E A Komech, I V Zvyagin, M V Pogorelyy, I Z Mamedov, D A Fedorenko, Y B Lebedev
Autologous hematopoietic stem cell transplantation (HSCT), a safer type of HSCT than allogeneic HSCT, is a promising therapy for patients with severe autoimmune diseases (ADs). Despite the long history of medical practice, structural changes in the adaptive immune system as a result of autologous HSCT in patients with various types of ADs remain poorly understood. In this study, we used high-throughput sequencing to investigate the structural changes in the peripheral blood T-cell repertoire in adult patients with ankylosing spondylitis (AS) during two years after autologous HSCT...
April 2018: Acta Naturae
Michelle Meyer, Asuka Yoshida, Palaniappan Ramanathan, Erica Ollmann Saphire, Peter L Collins, James E Crowe, Siba Samal, Alexander Bukreyev
Comparative immune response profiling is important for selecting next-generation vaccines. We comprehensively evaluated the antibody responses from a panel of nine respiratory vaccines against Ebola virus (EBOV) derived from human and avian paramyxoviruses expressing EBOV glycoprotein (GP). Most vaccines were protective in guinea pigs but yielded antibody repertoires that differed in proportion targeting key antigenic regions, avidity, neutralizing antibody specificities, and linear epitope preferences. Competition studies with monoclonal antibodies from human survivors revealed that some epitopes in GP targeted for neutralization were vector dependent, while EBOV-neutralizing titers correlated with the response magnitude toward the receptor-binding domain and GP1/GP2 interface epitopes...
August 14, 2018: Cell Reports
Eli B Nix, Joshua Choi, Christina Anthes, Gabrielle N Gaultier, Joelle Thorgrimson, Andrew D Cox, Raymond S W Tsang, William G McCready, Douglas Boreham, Marina Ulanova
During the last two decades, Haemophilus influenzae serotype a (Hia) emerged as an important cause of invasive disease in Canadian First Nations and Inuit, and Alaskan Native populations, with the highest rates reported in young children. Immunocompetent adults, in contrast to children, do not typically develop invasive Hia disease. To clarify factors responsible for an increased burden of invasive Hia disease in certain population groups we studied serum bactericidal activity (SBA) against Hia and quantified IgG and IgM specific to Hia capsular polysaccharide in healthy adult members of two First Nations communities: 1) with reported cases of invasive Hia disease (Northern Ontario, NO), and 2) without reported cases (Southern Ontario, SO), in comparison to non-First Nations living in proximity to the NO First Nations community, and non-First Nations elderly non-frail Canadians from across the country (total of 110 First Nations and 76 non-First Nations)...
2018: PloS One
Oren Avram, Anna Vaisman-Mentesh, Dror Yehezkel, Haim Ashkenazy, Tal Pupko, Yariv Wine
Reproducible and robust data on antibody repertoires are invaluable for basic and applied immunology. Next-generation sequencing (NGS) of antibody variable regions has emerged as a powerful tool in systems immunology, providing quantitative molecular information on antibody polyclonal composition. However, major computational challenges exist when analyzing antibody sequences, from error handling to hypermutation profiles and clonal expansion analyses. In this work, we developed the ASAP (A webserver for Immunoglobulin-Seq Analysis Pipeline) webserver (https://asap...
2018: Frontiers in Immunology
Georg Aue, Clare Sun, Delong Liu, Jae-Hyun Park, Stefania Pittaluga, Xin Tian, Elinor Lee, Susan Soto, Janet Valdez, Irina Maric, Maryalice Stetler-Stevenson, Constance Yuan, Yusuke Nakamura, Pawel Muranski, Adrian Wiestner
Immune stimulation contributes to lenalidomide's antitumor activity. Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature, autoreactive B cells in secondary lymphoid tissues, blood, and bone marrow and progressive immune dysfunction. Previous studies in CLL indicated that lenalidomide can repair defective T cell function in vitro. Whether T cell activation is required for clinical response to lenalidomide remains unclear. In this study, we report changes in the immune microenvironment in patients with CLL treated with single-agent lenalidomide and associate the immunologic effects of lenalidomide with antitumor response...
August 13, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Kathleen G Lanzer, Tres Cookenham, William W Reiley, Marcia A Blackman
Background: A diverse repertoire of naïve T cells is thought to be essential for a robust response to new infections. However, a key aspect of aging of the T cell compartment is a decline in numbers and diversity of peripheral naïve T cells. We have hypothesized that the age-related decline in naïve T cells forces the immune system to respond to new infections using cross-reactive memory T cells generated to previous infections that dominate the aged peripheral T cell repertoire. Results: Here we confirm that the CD8 T cell response of aged, influenza-naïve mice to primary infection with influenza virus is dominated by T cells that derive from the memory T cell pool...
2018: Immunity & Ageing: I & A
Julian Smazynski, John R Webb
Resident memory T cells (TRM ) are a recently identified subset of long-lived memory T cells that are characterized in terms of their unique surface phenotype combined with a non-recirculating pattern of localization to non-lymphoid, peripheral tissues. TRM have quickly become a key area of focus in understanding immune responses to microbial infection in so-called "barrier" tissues, and appear to be particularly critical for protection against repeat exposure at the same site. More recently, tumor-infiltrating T cells with canonical TRM features are being identified in human cancers, in particular cancers of epithelial origin, and their presence is broadly found to be associated with favorable long-term prognosis...
2018: Frontiers in Immunology
Nima Nouri, Steven H Kleinstein
During adaptive immune responses, activated B cells expand and undergo somatic hypermutation of their B cell receptor (BCR), forming a clone of diversified cells that can be related back to a common ancestor. Identification of B cell clones from high-throughput Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) data relies on computational analysis. Recently, we proposed an automated method to partition sequences into clonal groups based on single-linkage hierarchical clustering of the BCR junction region with length-normalized Hamming distance metric...
2018: Frontiers in Immunology
Susan DeWolf, Boris Grinshpun, Thomas Savage, Sai Ping Lau, Aleksandar Obradovic, Brittany Shonts, Suxiao Yang, Heather Morris, Julien Zuber, Robert Winchester, Megan Sykes, Yufeng Shen
Alloreactive T lymphocytes are the primary mediators of immune responses in transplantation, both in the graft-versus-host and host-versus-graft directions. While essentially all clones comprising the human T cell repertoire have been selected on self-peptide presented by self-human leukocyte antigens (self-HLAs), much remains to be understood about the nature of clones capable of responding to allo-HLA molecules. Quantitative tools to study these cells are critical to understand fundamental features of this important response; however, the large size and diversity of the alloreactive T cell repertoire in humans presents a great technical challenge...
August 9, 2018: JCI Insight
April R Giles, Lakshmanan Govindasamy, Suryanarayan Somanathan, James M Wilson
Recent clinical trials have demonstrated the potential of adeno-associated virus (AAV)-based vectors for treating rare diseases. However, significant barriers remain for the translation of these vectors into widely available therapies. In particular, exposure to the AAV capsid can generate an immune response of neutralizing antibodies. One approach to overcome this response is to map the AAV-specific neutralizing epitopes and rationally design an AAV capsid able to evade neutralization. To accomplish this, we isolated a monoclonal antibody against AAV9 following immunization of Balb/c mice and hybridoma screening...
August 8, 2018: Journal of Virology
Qiang Liu, Yong-Li Zhang, Wei Hu, Shou-Ping Hu, Zhuo Zhang, Xue-Hui Cai, Xi-Jun He
The molecular repertoire of porcine alveolar macrophages (PAMs) is greatly affected by the microenvironment they are exposed to, and specifically by inflammatory cytokines, such as interferon gamma (IFN-γ) released by activated lymphocytes, and microbial products, such as lipopolysaccharide (LPS). In our previous study, we found that IFN-γ- and LPS-activated PAMs (M1) could inhibit porcine reproductive and respiratory syndrome virus (PRRSV) replication. In this study, comprehensive analysis of the expression profiles of the genes associated with the polarization of M0-type PAMs (resting) toward M1 phenotypes (activated by IFN-γ and LPS) led to the following main results: 1) 1551 and 1823 genes were upregulated or downregulated in M1-type PAMs, respectively, compared with M0-type PAMs; 2) Among these, genes encoding ASS1 and CRTAM were the most upregulated and downregulated, respectively; 3) Genes involved in cytokine-cytokine receptor interaction and the JAK/STAT signaling pathway were significantly upregulated, suggesting their critical role in cellular activation; and 4) Genes involved in antigen proteolysis and presentation (immunoproteasome subunits), and inhibition of virus replication (host restriction factors) were significantly upregulated, emphasizing the critical role of these cytokines in immunity...
August 4, 2018: Biochemical and Biophysical Research Communications
Nufar Marcus, Tali Stauber, Atar Lev, Amos J Simon, Jerry Stein, Arnon Broides, Ido Somekh, Shlomo Almashanu, Raz Somech
Newborn screening (NBS) programs for severe combined immunodeficiency (SCID), using the TREC-based assay, have enabled early diagnosis, prompt treatment, and eventually changed the natural history of affected infants. Nevertheless, it was believed that some affected infants with residual T cell, such as patients with MHC II deficiency, will be misdiagnosed by this assay. A full immune workup and genetic analysis using direct Sanger sequencing and whole exome sequencing have been performed to a patient that was identified by the Israeli NBS program for SCID...
August 6, 2018: Immunologic Research
Jelka Pohar, Quentin Simon, Simon Fillatreau
CD4+ Foxp3+ T regulatory cells (Treg) are essential for the life of the organism, in particular because they protect the host against its own autoaggressive CD4+ Foxp3- T lymphocytes (Tconv). Treg distinctively suppress autoaggressive immunity while permitting efficient defense against infectious diseases. This split effect indicates that Treg activity is controlled in an antigen-specific manner. This specificity is achieved first by the formation of the Treg repertoire during their development, and second by their activation in the periphery...
2018: Frontiers in Immunology
Mei-Hua Hwang, Nikos Darzentas, Dorothee Bienzle, Peter F Moore, Jodi Morrison, Stefan M Keller
The ability to mount adaptive immune responses to a diverse array of pathogens is essential to maintaining the health of an individual. The outcome of adaptive immune responses is influenced by the pool of available lymphocyte antigen receptors. Understanding the composition and dynamics of immune repertoires is hence of relevance to characterizing physiologic immunological processes as well as understanding disease pathogenesis. The dog is increasingly recognized as a model for human disease. The objective of this study was to utilize NGS for comprehensive and unbiased analysis of the IGH repertoire in healthy dogs...
August 2018: Veterinary Immunology and Immunopathology
M Z Luo, T Xu, X H Xue, Y P Wang, P L Wu, X M Chen, X M Tang, X D Zhao, Z Y Zhang
Objective: To investigate the clinical, immunological, and molecular manifestations of nuclear factor kappa-B subunit 2 (NFκB2) gene mutation associated common variable immunodeficiency (CVID) . Methods: A 14-month-old boy diagnosed with NFκB2-mutated CVID was admitted into Children's Hospital of Chongqing Medical University in December 2015. The clinical manifestations, biochemical tests, immunological function, molecular features, treatment, and follow-up of the patient were analyzed. The Chinese and PUBMED databases were searched with the key words "NFκB2" and "immune deficiency" and related literatures were reviewed...
August 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Tin Sing Lam, Marian van de Meent, Erik W A Marijt, J H Frederik Falkenburg, Inge Jedema
OBJECTIVES: The importance of autologous T-cell responses in immune surveillance against acute myeloid leukemia (AML) remains unclear. Therefore, we investigated the presence and functional reactivity of autoreactive T-cell responses against autologous AML blasts. METHODS: T-cells purified from PB samples harvested from patients during first complete remission were stimulated with autologous AML material harvested at diagnosis. After 12-14 days of co-culture, the T-cells were restimulated with autologous AML cells, and leukemia-reactive T-cell clones were isolated based on their expression of the activation marker CD137...
August 4, 2018: European Journal of Haematology
Christian Schröter, Jan Beck, Simon Krah, Stefan Zielonka, Achim Doerner, Laura Rhiel, Ralf Günther, Lars Toleikis, Harald Kolmar, Björn Hock, Stefan Becker
In this study, we present a multiparameter screening procedure for the identification of target-specific antibodies with prescribed properties. Based on B cell receptor gene repertoires from transgenic rats, yeast surface display libraries were generated, and high-affinity human antibodies were readily isolated. We demonstrate that specific desirable features, i.e., species' cross-reactivity and a broad epitope coverage can be integrated into the screening procedure using high-throughput fluorescence-activated cell sorting...
August 3, 2018: Molecular Biotechnology
Sergi Luque, Marc Lúcia, Elena Crespo, Marta Jarque, Josep M Grinyó, Oriol Bestard
Emerging evidence suggests that donor-reactive memory B cells (mBC) play a key role inducing antibody-mediated rejection (ABMR) after solid organ transplantation and show a broader antigen repertoire than plasma cells thus, being potentially present even in absence of donor-specific antibodies. Therefore, the development of novel immune assays capable of quantifying circulating donor-reactive mBC in organ transplantation is highly warranted. We developed a novel HLA-specific B-cell FluoroSpot assay capable of enumerating multiple HLA-specific Antibody Secreting Cells (ASC) originated from circulating mBC after in-vitro polyclonal activation...
July 31, 2018: Journal of Immunological Methods
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