The Experts below are selected from a list of 66 Experts worldwide ranked by ideXlab platform

Mark P Hogarth - One of the best experts on this subject based on the ideXlab platform.

  • dimeric fcγr ectodomains as probes of the fc receptor function of anti influenza virus igg
    Journal of Immunology, 2016
    Co-Authors: Bruce Wines, Hillary A Vanderven, Sandra Esparon, Anne B Kristensen, Stephen J Kent, Mark P Hogarth
    Abstract:

    Ab-dependent Cellular cytotoxicity, phagocytosis, and Ag presentation are key mechanisms of action of Abs arising in vaccine or naturally acquired immunity, as well of therapeutic mAbs. Cells expressing the low-affinity FcγRs (FcγRII or CD32 and FcγRIII or CD16) are activated for these functions when receptors are aggregated following the binding of IgG-opsonized targets. Despite the diversity of the Fc receptor proteins, IgG ligands, and potential Responding Cell types, the induction of all FcγR-mediated responses by opsonized targets requires the presentation of multiple Fc regions in close proximity to each other. We demonstrated that such "near-neighbor" Fc regions can be detected using defined recombinant soluble (rs) dimeric low-affinity ectodomains (rsFcγR) that have an absolute binding requirement for the simultaneous engagement of two IgG Fc regions. Like Cell surface-expressed FcγRs, the binding of dimeric rsFcγR ectodomains to Ab immune complexes was affected by Ab subclass, presentation, opsonization density, Fc fucosylation, or mutation. The activation of an NK Cell line and primary NK Cells by human IgG-opsonized influenza A hemagglutinin correlated with dimeric rsFcγRIIIa binding activity but not with Ab titer. Furthermore, the dimeric rsFcγR binding assay sensitively detected greater Fc receptor activity to pandemic H1N1 hemagglutinin after the swine influenza pandemic of 2009 in pooled human polyclonal IgG. Thus these dimeric rsFcγR ectodomains are validated, defined probes that should prove valuable in measuring the immune-activating capacity of IgG Abs elicited by infection or vaccination or experimentally derived IgG and its variants.

John C. Cambier - One of the best experts on this subject based on the ideXlab platform.

  • Antigen receptor signaling : Integration of protein tyrosine kinase functions
    Oncogene, 1998
    Co-Authors: Idan Tamir, John C. Cambier
    Abstract:

    Antigen receptors on T and B Cells function to transduce signals leading to a variety of biologic responses minimally including antigen receptor editing, apoptotic death, developmental progression, Cell activation, proliferation and survival. The response to antigen depends upon antigen affinity and valence, involvement of coreceptors in signaling and differentiative stage of the Responding Cell. The requirement that these receptors integrate signals that drive an array of responses may explain their evolved structural complexity. Antigen receptors are composed of multiple subunits compartmentalized to provide antigen recognition and signal transduction function. In lieu of on-board enzymatic activity these receptors rely on associated Protein Tyrosine Kinases (PTKs) for their signaling function. By aggregating the receptors, and hence their appended PTKs, antigens induce PTK transphosphorylation, activating them to phosphorylate the receptor within conserved motifs termed Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) found in transducer subunits. The tyrosyl phosphorylated ITAMs then interact with Src Homology 2 (SH2) domains within the PTKs leading to their further activation. As receptor phosphorylation is amplified, other effectors, such as Shc, dock by virtue of SH2 binding, and serve, in-turn, as substrates for these PTKs. This sequence of events not only provides a signal amplification mechanism by combining multiple consecutive steps with positive feedback, but also allows for signal diversification by differential recruitment of effectors that provide access to distinct parallel downstream signaling pathways. The subject of antigen receptor signaling has been recently reviewed in depth (; ). Here we discuss the biochemical basis of antigen receptor signal transduction, using the B Cell receptor (BCR) as a paradigm, with specific emphasis on the involved PTKs. We review several specific mechanisms by which responses through these receptors are propagated and modified by accessory molecules, and discuss how signal amplification and diversification are achieved.

  • Antigen receptor signaling: integration of protein tyrosine kinase functions.
    Oncogene, 1998
    Co-Authors: Idan Tamir, John C. Cambier
    Abstract:

    Antigen receptors on T and B Cells function to transduce signals leading to a variety of biologic responses minimally including antigen receptor editing, apoptotic death, developmental progression, Cell activation, proliferation and survival. The response to antigen depends upon antigen affinity and valence, involvement of coreceptors in signaling and differentiative stage of the Responding Cell. The requirement that these receptors integrate signals that drive an array of responses may explain their evolved structural complexity. Antigen receptors are composed of multiple subunits compartmentalized to provide antigen recognition and signal transduction function. In lieu of on-board enzymatic activity these receptors rely on associated Protein Tyrosine Kinases (PTKs) for their signaling function. By aggregating the receptors, and hence their appended PTKs, antigens induce PTK transphosphorylation, activating them to phosphorylate the receptor within conserved motifs termed Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) found in transducer subunits. The tyrosyl phosphorylated ITAMs then interact with Src Homology 2 (SH2) domains within the PTKs leading to their further activation. As receptor phosphorylation is amplified, other effectors, such as Shc, dock by virtue of SH2 binding, and serve, in-turn, as substrates for these PTKs. This sequence of events not only provides a signal amplification mechanism by combining multiple consecutive steps with positive feedback, but also allows for signal diversification by differential recruitment of effectors that provide access to distinct parallel downstream signaling pathways. The subject of antigen receptor signaling has been recently reviewed in depth (DeFranco, 1997; Kurosaki, 1997). Here we discuss the biochemical basis of antigen receptor signal transduction, using the B Cell receptor (BCR) as a paradigm, with specific emphasis on the involved PTKs. We review several specific mechanisms by which responses through these receptors are propagated and modified by accessory molecules, and discuss how signal amplification and diversification are achieved.

Vasilis Vasiliou - One of the best experts on this subject based on the ideXlab platform.

  • Evolutionary divergence and functions of the human interleukin (IL) gene family
    Human Genomics, 2010
    Co-Authors: Chad Brocker, David Thompson, Akiko Matsumoto, Daniel W Nebert, Vasilis Vasiliou
    Abstract:

    Cytokines play a very important role in nearly all aspects of inflammation and immunity. The term 'interleukin' (IL) has been used to describe a group of cytokines with complex immunomodulatory functions -- including Cell proliferation, maturation, migration and adhesion. These cytokines also play an important role in immune Cell differentiation and activation. Determining the exact function of a particular cytokine is complicated by the influence of the producing Cell type, the Responding Cell type and the phase of the immune response. ILs can also have pro- and anti-inflammatory effects, further complicating their characterisation. These molecules are under constant pressure to evolve due to continual competition between the host's immune system and infecting organisms; as such, ILs have undergone significant evolution. This has resulted in little amino acid conservation between orthologous proteins, which further complicates the gene family organisation. Within the literature there are a number of overlapping nomenclature and classification systems derived from biological function, receptor-binding properties and originating Cell type. Determining evolutionary relationships between ILs therefore can be confusing. More recently, crystallographic data and the identification of common structural motifs have led to a more accurate classification system. To date, the known ILs can be divided into four major groups based on distinguishing structural features. These groups include the genes encoding the IL1-like cytokines, the class I helical cytokines (IL4-like, γ -chain and IL6/12-like), the class II helical cytokines (IL10-like and IL28-like) and the IL17-like cytokines. In addition, there are a number of ILs that do not fit into any of the above groups, due either to their unique structural features or lack of structural information. This suggests that the gene family organisation may be subject to further change in the near future.

Idan Tamir - One of the best experts on this subject based on the ideXlab platform.

  • Antigen receptor signaling : Integration of protein tyrosine kinase functions
    Oncogene, 1998
    Co-Authors: Idan Tamir, John C. Cambier
    Abstract:

    Antigen receptors on T and B Cells function to transduce signals leading to a variety of biologic responses minimally including antigen receptor editing, apoptotic death, developmental progression, Cell activation, proliferation and survival. The response to antigen depends upon antigen affinity and valence, involvement of coreceptors in signaling and differentiative stage of the Responding Cell. The requirement that these receptors integrate signals that drive an array of responses may explain their evolved structural complexity. Antigen receptors are composed of multiple subunits compartmentalized to provide antigen recognition and signal transduction function. In lieu of on-board enzymatic activity these receptors rely on associated Protein Tyrosine Kinases (PTKs) for their signaling function. By aggregating the receptors, and hence their appended PTKs, antigens induce PTK transphosphorylation, activating them to phosphorylate the receptor within conserved motifs termed Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) found in transducer subunits. The tyrosyl phosphorylated ITAMs then interact with Src Homology 2 (SH2) domains within the PTKs leading to their further activation. As receptor phosphorylation is amplified, other effectors, such as Shc, dock by virtue of SH2 binding, and serve, in-turn, as substrates for these PTKs. This sequence of events not only provides a signal amplification mechanism by combining multiple consecutive steps with positive feedback, but also allows for signal diversification by differential recruitment of effectors that provide access to distinct parallel downstream signaling pathways. The subject of antigen receptor signaling has been recently reviewed in depth (; ). Here we discuss the biochemical basis of antigen receptor signal transduction, using the B Cell receptor (BCR) as a paradigm, with specific emphasis on the involved PTKs. We review several specific mechanisms by which responses through these receptors are propagated and modified by accessory molecules, and discuss how signal amplification and diversification are achieved.

  • Antigen receptor signaling: integration of protein tyrosine kinase functions.
    Oncogene, 1998
    Co-Authors: Idan Tamir, John C. Cambier
    Abstract:

    Antigen receptors on T and B Cells function to transduce signals leading to a variety of biologic responses minimally including antigen receptor editing, apoptotic death, developmental progression, Cell activation, proliferation and survival. The response to antigen depends upon antigen affinity and valence, involvement of coreceptors in signaling and differentiative stage of the Responding Cell. The requirement that these receptors integrate signals that drive an array of responses may explain their evolved structural complexity. Antigen receptors are composed of multiple subunits compartmentalized to provide antigen recognition and signal transduction function. In lieu of on-board enzymatic activity these receptors rely on associated Protein Tyrosine Kinases (PTKs) for their signaling function. By aggregating the receptors, and hence their appended PTKs, antigens induce PTK transphosphorylation, activating them to phosphorylate the receptor within conserved motifs termed Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) found in transducer subunits. The tyrosyl phosphorylated ITAMs then interact with Src Homology 2 (SH2) domains within the PTKs leading to their further activation. As receptor phosphorylation is amplified, other effectors, such as Shc, dock by virtue of SH2 binding, and serve, in-turn, as substrates for these PTKs. This sequence of events not only provides a signal amplification mechanism by combining multiple consecutive steps with positive feedback, but also allows for signal diversification by differential recruitment of effectors that provide access to distinct parallel downstream signaling pathways. The subject of antigen receptor signaling has been recently reviewed in depth (DeFranco, 1997; Kurosaki, 1997). Here we discuss the biochemical basis of antigen receptor signal transduction, using the B Cell receptor (BCR) as a paradigm, with specific emphasis on the involved PTKs. We review several specific mechanisms by which responses through these receptors are propagated and modified by accessory molecules, and discuss how signal amplification and diversification are achieved.

Chad Brocker - One of the best experts on this subject based on the ideXlab platform.

  • Evolutionary divergence and functions of the human interleukin (IL) gene family
    Human Genomics, 2010
    Co-Authors: Chad Brocker, David Thompson, Akiko Matsumoto, Daniel W Nebert, Vasilis Vasiliou
    Abstract:

    Cytokines play a very important role in nearly all aspects of inflammation and immunity. The term 'interleukin' (IL) has been used to describe a group of cytokines with complex immunomodulatory functions -- including Cell proliferation, maturation, migration and adhesion. These cytokines also play an important role in immune Cell differentiation and activation. Determining the exact function of a particular cytokine is complicated by the influence of the producing Cell type, the Responding Cell type and the phase of the immune response. ILs can also have pro- and anti-inflammatory effects, further complicating their characterisation. These molecules are under constant pressure to evolve due to continual competition between the host's immune system and infecting organisms; as such, ILs have undergone significant evolution. This has resulted in little amino acid conservation between orthologous proteins, which further complicates the gene family organisation. Within the literature there are a number of overlapping nomenclature and classification systems derived from biological function, receptor-binding properties and originating Cell type. Determining evolutionary relationships between ILs therefore can be confusing. More recently, crystallographic data and the identification of common structural motifs have led to a more accurate classification system. To date, the known ILs can be divided into four major groups based on distinguishing structural features. These groups include the genes encoding the IL1-like cytokines, the class I helical cytokines (IL4-like, γ -chain and IL6/12-like), the class II helical cytokines (IL10-like and IL28-like) and the IL17-like cytokines. In addition, there are a number of ILs that do not fit into any of the above groups, due either to their unique structural features or lack of structural information. This suggests that the gene family organisation may be subject to further change in the near future.