The Experts below are selected from a list of 231 Experts worldwide ranked by ideXlab platform
Francisco Lozano - One of the best experts on this subject based on the ideXlab platform.
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Protective Effects of Human and Mouse Soluble Scavenger-Like CD6 Lymphocyte Receptor in a Lethal Model of Polymicrobial Sepsis.
Antimicrobial agents and chemotherapy, 2016Co-Authors: Mario Martínez-florensa, Marta Consuegra-fernández, Fernando Aranda, Noelia Armiger-borràs, Jordi Vila, Marianna Di Scala, Esther Carrasco, Jerónimo Pachón, Gloria González-aseguinolaza, Francisco LozanoAbstract:Sepsis still constitutes an unmet clinical need, which could benefit from novel adjunctive strategies to conventional antibiotic therapy. The soluble form of the scavenger-like human CD6 Lymphocyte Receptor (shCD6) binds to key pathogenic components from Gram-positive and -negative bacteria and shows time- and dose-dependent efficacy in mouse models of monobacterial sepsis. The objective of the present work was to demonstrate the effectiveness of infusing mouse and human sCD6 by different systemic routes, either alone or as adjunctive therapy to gold standard antibiotics, in a lethal model of polymicrobial sepsis. To this end, C57BL/6 mice undergoing high-grade septic shock induced by cecal ligation and puncture (CLP; ≥90% lethality) were infused via the intraperitoneal (i.p.) or intravenous (i.v.) route with shCD6 at different doses and time points, either alone or in combination with imipenem/cilastatin (I/C) at a dose of 33 mg/kg of body weight every 8 h. Significantly reduced mortality and proinflammatory cytokine levels were observed by i.p. infusion of a single shCD6 dose (1.25 mg/kg) 1 h pre- or post-CLP. When using the i.v. route, mice survival was significantly extended by starting shCD6 infusion at later time points post-CLP (up to 6 h after CLP). Significant adjunctive effects on mouse survival were observed by i.p. or i.v. infusion of shCD6 in combination with i.p. I/C post-CLP. Similar results were obtained in mice expressing high sustained levels (5 to 10 μg/ml) of mouse sCD6 in serum by means of transduction with hepatotropic adeno-associated virus (AAV). Taken together, the data support the conserved antibacterial effects of human and mouse sCD6 and their use as adjunctive therapy in experimental models of complex and severe polymicrobial sepsis.
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Targeting of Key Pathogenic Factors From Gram-Positive Bacteria by the Soluble Ectodomain of the Scavenger-Like Lymphocyte Receptor CD6
The Journal of infectious diseases, 2013Co-Authors: Mario Martínez-florensa, Marta Consuegra-fernández, Noelia Armiger-borràs, Vanesa G. Martínez, Olga Cañadas, Lizette Bonet-roselló, Aina Farran, Jordi Vila, Cristina Casals, Francisco LozanoAbstract:Gram-positive bacteria cause a broad spectrum of infection-related diseases in both immunocompetent and immunocompromised hosts, ranging from localized infections to severe systemic conditions such as septic and toxic shock syndromes. This situation has been aggravated by the recent emergence of multidrug-resistant strains, thus stressing the need for alternative therapeutic approaches. One such possibility would be modulating the host's immune response. Herein, the potential use of a soluble form of the scavenger-like human Lymphocyte Receptor CD6 (shCD6) belonging to an ancient family of innate immune Receptors has been evaluated. shCD6 can bind to a broad spectrum of gram-positive bacteria thanks to the recognition of highly conserved cell wall components (lipoteichoic acid [LTA] and peptidoglycan [PGN]), which are essential for their viability and pathogenicity and are not amenable to antibiotic resistance. shCD6 has in vitro inhibitory effects on both bacterial growth and Toll-like Receptor-mediated inflammatory response induced by LTA plus PGN. In vivo infusion of shCD6 improves survival on mouse models of septic shock by Staphylococcus aureus (either multidrug-resistant or -sensitive) or their endotoxins (LTA + PGN) or exotoxins (TSST-1). These results support the use of shCD6 and/or other scavenger-like immune Receptors in the treatment of severe gram-positive-induced infectious conditions.
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the immunomodulatory properties of the cd5 Lymphocyte Receptor in health and disease
Current Opinion in Immunology, 2011Co-Authors: Gloria Soldevila, Chander Raman, Francisco LozanoAbstract:CD5 is a scavenger-like Receptor expressed in association with the antigen-specific Receptors on T and B-1a Lymphocytes. Recent studies reveal a broader biology for CD5 that includes its role as regulator of cell death and as a Receptor for pathogen-associated molecular patterns, in addition to its previously described function as an inhibitory Receptor. These findings shed new light into the mechanistic role of CD5 in leukemias and effector cells to exogenous (infectious) or endogenous (autoimmune, tumoral) antigens. The newly identified properties make this Receptor a potential candidate to be targeted for therapeutic intervention as well as immune modulation. This review describes the current knowledge on the function of CD5 as an immunomodulatory Receptor both in health and in disease.
Steven H Kleinstein - One of the best experts on this subject based on the ideXlab platform.
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presto a toolkit for processing high throughput sequencing raw reads of Lymphocyte Receptor repertoires
Bioinformatics, 2014Co-Authors: Jason Vander A Heiden, Gur Yaari, Mohamed Uduman, Joel N H Stern, Kevin C Oconnor, David A Hafler, Francois Vigneault, Steven H KleinsteinAbstract:Summary: Driven by dramatic technological improvements, large-scale characterization of Lymphocyte Receptor repertoires via high-throughput sequencing is now feasible. Although promising, the high germline and somatic diversity, especially of B-cell immunoglobulin repertoires, presents challenges for analysis requiring the development of specialized computational pipelines. We developed the REpertoire Sequencing TOolkit (pRESTO) for processing reads from high-throughput Lymphocyte Receptor studies. pRESTO processes raw sequences to produce error-corrected, sorted and annotated sequence sets, along with a wealth of metrics at each step. The toolkit supports multiplexed primer pools, single- or paired-end reads and emerging technologies that use single-molecule identifiers. pRESTO has been tested on data generated from Roche and Illumina platforms. It has a built-in capacity to parallelize the work between available processors and is able to efficiently process millions of sequences generated by typical high-throughput projects. Availability and implementation: pRESTO is freely available for academic use. The software package and detailed tutorials may be downloaded from http://clip.med.yale.edu/presto. Contact: ude.elay@nietsnielk.nevets Supplementary information: Supplementary data are available at Bioinformatics online.
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pRESTO: a toolkit for processing high-throughput sequencing raw reads of Lymphocyte Receptor repertoires (TECH1P.863)
Journal of Immunology, 2014Co-Authors: Jason A. Vander Heiden, Gur Yaari, Mohamed Uduman, Joel N H Stern, Francois Vigneault, Kevin C. O’connor, David Halfer, Steven H KleinsteinAbstract:Summary: Driven by dramatic technological improvements, large-scale characterization of Lymphocyte Receptor repertoires via high-throughput sequencing is now feasible. Although promising, the high germline and somatic diversity, especially of B-cell immunoglobulin repertoires, presents challenges for analysis requiring the development of specialized computational pipelines. We developed the REpertoire Sequencing TOolkit (pRESTO) for processing reads from high-throughput Lymphocyte Receptor studies. pRESTO processes raw sequences to produce error-corrected, sorted and annotated sequence sets, along with a wealth of metrics at each step. The toolkit supports multiplexed primer pools, single- or paired-end reads, and emerging technologies that employ single-molecule barcodes. pRESTO has been tested on data generated from Roche and Illumina platforms. It has a built in capacity to parallelize the work between available processors, and is able to efficiently process millions of sequences generated by typical high-throughput projects. As part of ongoing collaborations, pRESTO has been applied to multiple B-cell repertoire studies, employing both Roche 454 and Illumina MiSeq sequencing technologies. Availability: pRESTO is freely available for academic use. The software package and detailed tutorials may be downloaded from http://clip.med.yale.edu/pRESTO.
Eric Hsu - One of the best experts on this subject based on the ideXlab platform.
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cdw150 slam is a Receptor for a lymphotropic strain of measles virus and may account for the immunosuppressive properties of this virus
Virology, 2001Co-Authors: Eric Hsu, Caterina Iorio, Farida Sarangi, Aye Aye Khine, Christopher D RichardsonAbstract:Abstract Natural isolates of measles virus readily infect several Lymphocyte cell lines. These viruses appear to use a Receptor other than CD46, the molecule to which most laboratory strains of virus bind. Methods used to identify and characterize this Lymphocyte Receptor for measles virus are described in this study. A binding assay with a soluble form of measles virus H protein demonstrated that B-cell lines, activated with Epstein–Barr virus, or T cells, transformed with human T-cell leukemia virus, exhibit this Receptor on their cell surfaces. On the other hand, resting Lymphocytes, monocytes, or immature leukocytes either failed to express or possessed reduced levels of this Receptor. A cDNA library derived from B95-8 marmoset B-cell lines was used to identify this Receptor through expression cloning. This molecule was shown to be CDw150, which is also known as the signaling lymphocytic activation molecule (SLAM). When the Lymphocyte Receptor was expressed in Chinese hamster ovary (CHOP) or human embryonic kidney (293T) cells, these cells became susceptible to lymphotropic as well as laboratory strains of measles virus. Binding assays confirmed that either lymphotropic or laboratory strains of measles virus could adhere to human or marmoset CDw150, but interaction with the mouse homolog was weak. These infections were independent of the presence of CD46 on the host cell surface. Interaction of measles virus with CDw150(SLAM) could explain the immunosuppressive properties of this virus.
Tae Sung Jung - One of the best experts on this subject based on the ideXlab platform.
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characterization of hagfish eptatretus burgeri variable Lymphocyte Receptor based antibody and its potential role in the neutralization of nervous necrosis virus
Journal of Immunology, 2020Co-Authors: Jae Wook Jung, Jassy Mary S Lazarte, Jin Hong Chun, Kim D Thompson, Se Pyeong Im, Min Woo Ha, Tae Sung JungAbstract:: The variable Lymphocyte Receptor (VLR) mediates the humoral immune response in jawless vertebrates, including lamprey (Petromyzon marinus) and hagfish (Eptatretus burgeri). Hagfish VLRBs are composed of leucine-rich repeat (LRR) modules, conjugated with a superhydrophobic C-terminal tail, which contributes to low levels of expression in recombinant protein technology. In this study, we screened Ag-specific VLRBs from hagfish immunized with nervous necrosis virus (NNV). The artificially multimerized form of VLRB was constructed using a mammalian expression system. To enhance the level of expression of the Ag-specific VLRB, mutagenesis of the VLRB was achieved in vitro through domain swapping of the LRR C-terminal cap and variable LRR module. The mutant VLRB obtained, with high expression and secretion levels, was able to specifically recognize purified and progeny NNV, and the Ag binding ability of this mutant was increased by at least 250-fold to that of the nonmutant VLRB. Furthermore, preincubation of the Ag-specific VLRB with NNV reduced the infectivity of NNV in E11 cells in vitro, and in vivo experiment. Our results suggest that the newly developed Ag-specific VLRB has the potential to be used as diagnostic and therapeutic reagents for NNV infections in fish.
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development of a modified yeast display system for screening antigen specific variable Lymphocyte Receptor b in hagfish eptatretus burgeri
Journal of Immunological Methods, 2019Co-Authors: Jaesung Kim, Jung Seok Lee, Si Won Kim, Jae Wook Jung, Jassy Mary S Lazarte, Young Rim Kim, Jin Hong Chun, Jong Pyo Suh, Kim D Thompson, Tae Sung JungAbstract:The variable Lymphocyte Receptor B (VLRB) of jawless vertebrates has a similar function to the antibodies produced by jawed vertebrates, and has been considered as an alternative source to mammalian antibodies for use in biological research. We developed a modified yeast display vector system (pYD8) to display recombinant hagfish VLRB proteins on the extracellular surface of yeast for the isolation of antigen-specific VLRBs. After observing an up-regulation in the VLRB response in hagfish immunized with hemagglutinin 1 of avian influenza virus H9N2 subtype (H9N2-HA1), the antigen-specific VLRBs decorated on the yeast's surface were selected by quantitative library screening through magnetic-activated cell sorting (MACS) and fluorescent-activated cell sorting (FACS). We also demonstrated a strong specificity of the antigen-specific VLRBs, when expressed as a secreted protein using a mammalian expression system. Together, our findings suggest that the pYD8 vector system could be useful for screening antigen-specific hagfish VLRBs, and the specificity of secreted VLRB may have potential for a variety of biological applications.
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potential use of genetically engineered variable Lymphocyte Receptor b specific to avian influenza virus h9n2
Journal of Immunology, 2018Co-Authors: Jaesung Kim, Jung Seok Lee, Si Won Kim, Jae Wook Jung, Jassy Mary S Lazarte, Jong Yong Kim, Young Rim Kim, Jeongho Lee, Roger S M Chong, Tae Sung JungAbstract:The variable Lymphocyte Receptor (VLR) B of jawless vertebrates functions as a secreted Ab of jawed vertebrates and has emerged as an alternative Ab with a single polypeptide chain. After observing an upregulated VLRB response in hagfish immunized with avian influenza virus (AIV) subtype H9N2, we screened AIV H9N2-specific VLRB using a mammalian expression system. To improve the binding avidity of the Ag-specific VLRB to the Ag, we enabled multimerization of the VLRB by conjugating it with C-terminal domain of human C4b-binding protein. To dramatically enhance the expression and secretion of the Ag-specific VLRB, we introduced a glycine-serine linker and the murine Ig κ leader sequence. The practical use of the Ag-specific VLRB was also demonstrated through various immunoassays, detected by anti-VLRB Ab (11G5). Finally, we found that the Ag-specific VLRB decreased the infectivity of AIV H9N2. Together, our findings suggest that the generated Ag-specific VLRB could be used for various immunoapplications.
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expression and characterization of monomeric variable Lymphocyte Receptor b specific to the glycoprotein of viral hemorrhagic septicemia virus vhsv
Journal of Immunological Methods, 2018Co-Authors: Jung Seok Lee, Jaesung Kim, Si Won Kim, Jae Wook Jung, Jassy Mary S Lazarte, Jeongho Lee, Kim D Thompson, Tae Sung JungAbstract:Abstract Monomeric variable Lymphocyte Receptor B (VLRB) is one of the smallest binding scaffold (20–25 kDa) from jawless vertebrates, hagfish and lamprey. This relatively new class of binding scaffold has various advantages: i) it has a single peptide composition, amenable to molecular engineering for enhancing its stability and affinity; ii) it has a small size, contributing better tissue penetration and easier production using microorganism expression system. Monomeric arVLRB142, which can specifically bind to the glycoprotein of viral hemorrhagic septicemia virus (VHSV), was expressed in Pichia pastoris. High quantity recombinant monomeric arVLRB142 (rVLR142mono) was purified from 100 ml of culture with a resulting yield of 2.6 ±1.3 mg of target protein. Functional studies revealed that the purified rVLR142mono can specifically recognize low levels of the target antigen (recombinant glycoprotein) (i.e. as low as 0.1 nM), but also the native glycoprotein of VHSV. The expressed rVLR142mono exhibited high levels of stability and it retained it binding capacity over broad temperature (4 °C ~ 60 °C) and pH ranges (pH 1.5–12.5). We developed an effective expression system for mass production of monomeric VLRB based on P. pastoris. The recombinant protein that was obtained offers promising binding avidity and biophysical stability and its potential use in various biotechnological applications.
José R. Regueiro - One of the best experts on this subject based on the ideXlab platform.
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T Lymphocyte Receptor deficiencies.
Current Opinion in Immunology, 1995Co-Authors: Dietmar J. Kappes, Balbino Alarcon, José R. RegueiroAbstract:Signalling through the TCR is mediated by the cytoplasmic tails of the CD3 complex. Deficiencies in the expression of different CD3 components have lead to dramatic, yet dissimilar, effects on T-cell development and to selective deficits in peripheral T-cell subsets. Recent studies of human patients and animal models with CD3 deficiencies are providing insights into the redundant and unique roles of these molecules.
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A diallelic RFLP of the CD3-epsilon chain of the clonotypic T-Lymphocyte Receptor is not associated with certain autoimmune diseases
Human Genetics, 1991Co-Authors: Marcos Timon, Paloma Pérez-aciego, Djamal Benmamar, Pablo Morales, Antonio Arnaiz-villena, José R. RegueiroAbstract:A diallelic restriction fragment length polymorphism of the CD3-epsilon (ɛ) gene, which encodes for an invariant component of the human T-Lymphocyte Receptor, is observed when using genomic DNA Taq I digests probed with a CD3-ɛ chain cDNA probe. This combination shows two alleles of 9.1 kb and 8.4 kb with a frequency of 0.66 and 0.34, respectively, in the Spanish population. None of these alleles is associated with susceptibility to juvenile rheumatoid arthritis (JRA) or insulin-dependent diabetes mellitus (IDDM).
