Modulation of immune response by combined targeting of complement receptors and low-affinity Fcgamma receptors. 2010

Zsuzsanna Szekeres, and Melinda Herbáth, and Adrienn Angyal, and Zoltán Szittner, and Viktor Virág, and Péter Balogh, and Anna Erdei, and József Prechl
Department of Immunology, Eötvös Loránd University, Budapest, Hungary.

Immune complexes (ICs) induce effective pathogen-specific innate and humoral immune response via immunecomplex-binding receptors, such as murine complement receptor type 1 and 2 (mCR1/2) and murine low-affinity Fc receptors for IgG (mFcgammaRII and III). The exact function of mCR1/2 in cooperation with mFcgammaRII/III in modulation of humoral immunity has not yet been adequately clarified. The aim of this study was to target these receptors by specific single-chain fragments of antibody (scFv), either individually or in combination, thus modelling the action of IC. For targeting, we used scFv derived from the well-characterized 7g6 and 2.4g2 monoclonal antibodies recognizing mCR1/2 and mFcgammaRII/III, respectively. These scFvs were monobiotinylated and conjugated to streptavidin or streptavidin-coated microspheres. Such complexes were investigated with respect to target receptor recognition and in vivo localization. Antibody response against the constructs was measured by ELISA and ELISPOT. Results show that targeting streptavidin complexes to mFcgammaRII/III induces stronger IgG1 response than targeting to mCR1/2 yet both strategies enhance the antibody response compared to the control group immunized with non-targeted peptide-streptavidin complexes. Moreover, the immunogenicity of coupled antigens increased using microspheres as carrier, instead of using soluble streptavidin. In summery, our in vivo experiments reveal that mFcgammaRII/III is more potent a target than CR1/2 and show that combined targeting of CR1/2 and FcgammaRII/III receptors does not result in cumulative enhancement of the antigen specific immune response. In addition, microparticle-mediated enhancement of immunization can be further improved by FcgammaRII/III targeting.

UI MeSH Term Description Entries
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D011951 Receptors, Complement Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement. Complement Receptors,Complement Receptor,Complement Receptor Type 1,Receptor, Complement
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D005260 Female Females
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000936 Antigen-Antibody Complex The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES. Immune Complex,Antigen-Antibody Complexes,Immune Complexes,Antigen Antibody Complex,Antigen Antibody Complexes,Complex, Antigen-Antibody,Complex, Immune,Complexes, Antigen-Antibody,Complexes, Immune
D017452 Receptors, IgG Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor). Antigens, CD16,Antigens, CD32,Antigens, CD64,CD16 Antigens,CD32 Antigens,CD64 Antigen,CD64 Antigens,Fc Gamma Receptor,Fc Receptors, gamma,Fc gamma Receptors,IgG Receptor,IgG Receptors,Leu-11 Antigen,Receptors, Fc gamma,gamma Fc Receptor,gamma Fc Receptors,CD 16 Antigens,CD 32 Antigens,CD 64 Antigens,CDw32 Antigens,Fc gamma RI,Fc gamma RII,Fc gamma RIII,Immunoglobulin G Receptor,Leu-11 Antigens,Antigen, CD64,Antigen, Leu-11,Antigens, CD 16,Antigens, CD 32,Antigens, CD 64,Antigens, CDw32,Antigens, Leu-11,Fc Receptor, gamma,Gamma Receptor, Fc,Leu 11 Antigen,Leu 11 Antigens,Receptor, Fc Gamma,Receptor, IgG,Receptor, Immunoglobulin G,Receptor, gamma Fc,Receptors, gamma Fc,gamma RI, Fc,gamma RII, Fc,gamma RIII, Fc,gamma Receptors, Fc
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D056724 Immunity, Humoral Antibody-mediated immune response. Humoral immunity is brought about by ANTIBODY FORMATION, resulting from TH2 CELLS activating B-LYMPHOCYTES, followed by COMPLEMENT ACTIVATION. Humoral Immune Response,Humoral Immune Responses,Humoral Immunity,Immune Response, Humoral,Immune Responses, Humoral,Response, Humoral Immune

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