The Experts below are selected from a list of 63 Experts worldwide ranked by ideXlab platform

Jenny M Woof - One of the best experts on this subject based on the ideXlab platform.

  • the human iga fc α receptor interaction and its blockade by Streptococcal iga binding Proteins
    Biochemical Society Transactions, 2002
    Co-Authors: Jenny M Woof
    Abstract:

    IgA plays a key role in immune defence of the mucosal surfaces. IgA can trigger elimination mechanisms against pathogens through the interaction of its Fc region with FcαRs (receptors specific for the Fc region of IgA) present on neutrophils, macrophages, monocytes and eosinophils. The human FcαR (CD89) shares homology with receptors specific for the Fc region of IgG (FcαRs) and IgE (FcαRIs), but is a more distantly related member of the receptor family. CD89 interacts with residues lying at the interface of the two domains of IgA Fc, a site quite distinct from the homologous regions at the top of IgG and IgE Fc recognized by FcαR and FcαRI respectively. Certain pathogenic bacteria express surface Proteins that bind to human IgA Fc. Experiments with domain-swap antibodies and mutant IgAs indicate that binding of three such Proteins (Sir22 and Arp4 of Streptococcus pyogenes and β protein of group B streptococci) depend on sites in the Fc interdomain region of IgA, the binding region also used by CD89. Further, we have found that the Streptococcal Proteins can inhibit interaction of IgA with CD89, and have thereby identified a mechanism by which a bacterial IgA-binding protein may modulate IgA effector function.

  • Streptococcal iga binding Proteins bind in the cα2 cα3 interdomain region and inhibit binding of iga to human cd89
    Journal of Biological Chemistry, 2001
    Co-Authors: Richard J Pleass, Thomas Areschoug, Gunnar Lindahl, Jenny M Woof
    Abstract:

    Abstract Certain pathogenic bacteria express surface Proteins that bind to the Fc part of human IgA or IgG. These bacterial Proteins are important as immunochemical tools and model systems, but their biological function is still unclear. Here, we describe studies of three Streptococcal Proteins that bind IgA: the Sir22 and Arp4 Proteins of Streptococcus pyogenes and the unrelated β protein of group B streptococcus. Analysis of IgA domain swap and point mutants indicated that two loops at the Cα2/Cα3 domain interface are critical for binding of the Streptococcal Proteins. This region is also used in binding the human IgA receptor CD89, an important mediator of IgA effector function. In agreement with this finding, the three IgA-binding Proteins and a 50-residue IgA-binding peptide derived from Sir22 blocked the ability of IgA to bind CD89. Further, the Arp4 protein inhibited the ability of IgA to trigger a neutrophil respiratory burst via CD89. Thus, we have identified residues on IgA-Fc that play a key role in binding of different Streptococcal IgA-binding Proteins, and we have identified a mechanism by which a bacterial IgA-binding protein may interfere with IgA effector function.

Gunnar Lindahl - One of the best experts on this subject based on the ideXlab platform.

  • Streptococcal iga binding Proteins bind in the cα2 cα3 interdomain region and inhibit binding of iga to human cd89
    Journal of Biological Chemistry, 2001
    Co-Authors: Richard J Pleass, Thomas Areschoug, Gunnar Lindahl, Jenny M Woof
    Abstract:

    Abstract Certain pathogenic bacteria express surface Proteins that bind to the Fc part of human IgA or IgG. These bacterial Proteins are important as immunochemical tools and model systems, but their biological function is still unclear. Here, we describe studies of three Streptococcal Proteins that bind IgA: the Sir22 and Arp4 Proteins of Streptococcus pyogenes and the unrelated β protein of group B streptococcus. Analysis of IgA domain swap and point mutants indicated that two loops at the Cα2/Cα3 domain interface are critical for binding of the Streptococcal Proteins. This region is also used in binding the human IgA receptor CD89, an important mediator of IgA effector function. In agreement with this finding, the three IgA-binding Proteins and a 50-residue IgA-binding peptide derived from Sir22 blocked the ability of IgA to bind CD89. Further, the Arp4 protein inhibited the ability of IgA to trigger a neutrophil respiratory burst via CD89. Thus, we have identified residues on IgA-Fc that play a key role in binding of different Streptococcal IgA-binding Proteins, and we have identified a mechanism by which a bacterial IgA-binding protein may interfere with IgA effector function.

  • vaccination with highly purified cell surface Proteins confers protection against experimental group b Streptococcal infection
    Advances in Experimental Medicine and Biology, 1997
    Co-Authors: Charlotte Larsson, Margaretha Stalhammarcarlemalm, Gunnar Lindahl
    Abstract:

    Group B Streptococcus (GBS) is the major cause of invasive bacterial infections among neonates. Although the polysaccharide capsule of GBS has attracted the most attention with regard to vaccine development, there is evidence that bacterial surface Proteins may also confer protective immunity.3 Previous work has shown that ≈90% of all GBS strains causing invasive infections express either protein Rib or protein α on the cell surface.3 The Rib and α Proteins are structurally related and define a novel family of Streptococcal Proteins, which in vitro show little or no cross-reactivity immunologically.2, 3, 4 To analyze whether these Proteins can be used for vaccination against GBS disease, we developed a method for isolation of these Proteins in a highly purified form, free of polysaccharides. Here we summarize data from our experiments which demonstrate that active immunization with each of these purified Proteins protects mice from lethal infection with GBS strains expressing the corresponding protein.2

Guido Grandi - One of the best experts on this subject based on the ideXlab platform.

  • capturing host pathogen interactions by protein microarrays identification of novel Streptococcal Proteins binding to human fibronectin fibrinogen and c4bp
    The FASEB Journal, 2009
    Co-Authors: Immaculada Margarit, Stefano Bonacci, Giampiero Pietrocola, Simonetta Rindi, Claudia Ghezzo, Mauro Bombaci, Vincenzo Nardidei, Renata Grifantini, Pietro Speziale, Guido Grandi
    Abstract:

    Microbial pathogen entry and survival in the host is mediated by a network of molecular interactions between the two partners, which has been the subject of many research efforts. A complex picture is emerging in which host-pathogen crosstalk involves a high number of Proteins, often with redundant functions. In the present study, we investigated the potential of protein microarrays to simultaneously scan interactions between surface Proteins from two main human Streptococcal pathogens, Streptococcus pyogenes and Streptococcus agalactiae, and three human ligands, fibronectin, fibrinogen, and C4 binding protein, known to play an important role in Streptococcal pathogenesis. By using this technology, we confirmed interactions described in the literature and detected a novel set of Streptococcal Proteins with binding capacities for the human ligands. The observations were validated by Western blot and ELISA techniques. Three of the newly identified Proteins were isoforms of a group B streptococcus-secreted c...

Richard J Pleass - One of the best experts on this subject based on the ideXlab platform.

  • Streptococcal iga binding Proteins bind in the cα2 cα3 interdomain region and inhibit binding of iga to human cd89
    Journal of Biological Chemistry, 2001
    Co-Authors: Richard J Pleass, Thomas Areschoug, Gunnar Lindahl, Jenny M Woof
    Abstract:

    Abstract Certain pathogenic bacteria express surface Proteins that bind to the Fc part of human IgA or IgG. These bacterial Proteins are important as immunochemical tools and model systems, but their biological function is still unclear. Here, we describe studies of three Streptococcal Proteins that bind IgA: the Sir22 and Arp4 Proteins of Streptococcus pyogenes and the unrelated β protein of group B streptococcus. Analysis of IgA domain swap and point mutants indicated that two loops at the Cα2/Cα3 domain interface are critical for binding of the Streptococcal Proteins. This region is also used in binding the human IgA receptor CD89, an important mediator of IgA effector function. In agreement with this finding, the three IgA-binding Proteins and a 50-residue IgA-binding peptide derived from Sir22 blocked the ability of IgA to bind CD89. Further, the Arp4 protein inhibited the ability of IgA to trigger a neutrophil respiratory burst via CD89. Thus, we have identified residues on IgA-Fc that play a key role in binding of different Streptococcal IgA-binding Proteins, and we have identified a mechanism by which a bacterial IgA-binding protein may interfere with IgA effector function.

A V Powles - One of the best experts on this subject based on the ideXlab platform.

  • Selective response of dermal Th-1 cells to 20-50 kDa Streptococcal cell-wall Proteins in chronic plaque psoriasis.
    Scandinavian Journal of Immunology, 2003
    Co-Authors: B S Baker, Vincent A Fischetti, J M Ovigne, A V Powles
    Abstract:

    We have recently described a dermal Th-1 subset in skin lesions of psoriasis which recognizes cell-wall extract isolated from group A streptococci (GAS). As a first step in the identification of the Streptococcal Proteins involved, dermal T-cell lines (TCL) cultured from the lesional skin of 12 human leucocyte antigen (HLA)-typed psoriasis patients were stimulated with GAS cell-wall extract and 14 fractions (MWt approximately 20–100 kDa) separated from the cell-wall extract by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and electroelution, stained for intracellular interferon-γ(IFN-γ) expression and analysed by flow cytometry. All the TCL responded to GAS cell-wall extract to varying extents (3.5–27.6% IFN-γ+). This response was consistently directed against 20–50 kDa cell-wall fractions and inhibited by anti-HLA-DR antibody. TCL with higher responses to GAS cell-wall extract recognized a larger number of fractions within this range than the lower responder TCL. No difference between the level and pattern of response to the fractions was observed for TCL from HLA-DR7+ (n = 6) and HLA-DR7– (n = 6) individuals. This preliminary study has shown a selective response to lower MWt Proteins expressed on GAS cell wall by skin Th-1 cells in psoriasis. Further studies are required to identify the Proteins involved.

  • stronger proliferative response to membrane versus cell wall Streptococcal Proteins by peripheral blood t cells in chronic plaque psoriasis
    Scandinavian Journal of Immunology, 2001
    Co-Authors: B S Baker, Dean W Brown, Vincent A Fischetti, J M Ovigne, W Porter, A V Powles
    Abstract:

    Proliferative responses of peripheral blood mononuclear cells (PBMC) to group A Streptococcal (GAS) antigens have been studied in 24 patients with psoriasis and 15 disease controls. Extracts of cell wall (including M protein) from types M4 and M12 GAS, recombinant M6 protein, and both cell-wall and cell-membrane extracts from type M6 (M6+) GAS and its corresponding M gene deletion mutant (M6-) were tested. PBMC from psoriatic patients proliferated more strongly to cell-wall extracts from M12 versus M4 (P = 0.0348), and to M6+ versus M6- (P = 0.0019) GAS with, in most cases, moderate proliferation to recombinant M6 protein. The psoriatic response to M12 cell wall was significantly increased compared to the controls (P = 0.0032). In psoriatics, M6+ membrane extracts induced a markedly greater proliferation than those of cell wall (P = 0.0002); responses to M6+ (P = 0.0039) and M6- (P = 0.0114) membrane extracts were higher than those of the control PBMC. Both groups showed a decreased response to the M6- versus M6+ membrane extracts (P = 0.0030; P= 0.0181, respectively). This study has demonstrated that patients with psoriasis have a heightened circulating T-cell response to cell wall M protein and to non-M Proteins present on the cell wall and membrane of GAS.