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      Anti-Ids in Allergy: Timeliness of a Classic Concept

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          Abstract

          Abstract:

          Anti-idiotypic antibodies (anti-ids) are part of natural immune responses with regulatory capacity. Their effect on an antigen-specific, so-called Ab1 antibody response, is dependent on 1) the original antigen, which they mirror, being Ab2 antibodies, and 2) their isotype. In the case of IgE-mediated allergy, natural anti-ids against allergen-specific IgE represent internal images of allergen molecules. A key biologic feature of allergens is that they can crosslink IgE, expressed by B-lymphocytes or passively bound via high affinity receptors to effector cells, which renders cellular activation. Therefore, the IgE cross linking capability of anti-ids determines whether they dampen or enhance immediate-type hypersensitivity. Correspondingly to classic antiallergen blocking IgG antibodies, anti-ids may also interact with inhibitory FcγRIIb receptors and, thereby, down-regulate T H2-type inflammation. Anti-ids and other B-cell epitope mimetics, like mimotopes and DARPins, represent antigen surrogates, which can be used for vaccination. Intriguingly, they may induce antibody responses without activating potentially proinflammatory, antiallergen T-lymphocytes. Taken together, collective evidence suggests that anti-ids, although representing immunologic classics, are a timeless concept in allergology.

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          Most cited references52

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          Synthetic peptide vaccine design: synthesis and properties of a high-density multiple antigenic peptide system.

          J P Tam (1988)
          A convenient and versatile approach to the direct synthesis of a peptide-antigen matrix by the solid-phase method is described. The approach is called the multiple antigen peptide system (MAP) and it utilizes a simple scaffolding of a low number of sequential levels (n) of a trifunctional amino acid as the core matrix and 2n peptide antigens to form a macromolecule with a high density of peptide antigens of final Mr 10,000. The MAP model chosen for study was an octa-branching MAP consisting of a core matrix made up of three levels of lysine and eight amino terminals for anchoring peptide antigens. The MAP, containing both the core matrix and peptides of 9-16 amino acids, was prepared in a single synthesis by the solid-phase method. Six different MAPs elicited specific antibodies in rabbits and mice, of which five produced antibodies that reacted with their corresponding native proteins. In rabbits, the sera had a considerably higher titer of antibodies than sera prepared from the same peptides anchored covalently to keyhole limpet hemocyanin as carrier. Thus, the MAP provided a general, but chemically unambiguous, approach for the preparation of carrier-bound antigens of predetermined and reproducible structure and might be suitable for generating vaccines.
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            DARPins: a new generation of protein therapeutics.

            DARPins (designed ankyrin repeat proteins) are a novel class of binding molecules with the potential to overcome limitations of monoclonal antibodies, hence allowing novel therapeutic approaches. DARPins are small, single domain proteins (14 kDa) which can be selected to bind any given target protein with high affinity and specificity. These characteristics make them ideal agonistic, antagonistic or inhibitory drug candidates. Furthermore, DARPins can be engineered to carry various effector functions or combine multiple binding specificities, enabling completely new drug formats. Taken together, DARPins are a prominent member of the next generation of protein therapeutics with the potential to surpass existing antibody drugs.
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              FcgammaRIIb controls bone marrow plasma cell persistence and apoptosis.

              The survival of long-lived plasma cells, which produce most serum immunoglobulin, is central to humoral immunity. We found here that the inhibitory Fc receptor FcgammaRIIb was expressed on plasma cells and controlled their persistence in the bone marrow. Crosslinking FcgammaRIIb induced apoptosis of plasma cells, which we propose contributes to the control of their homeostasis and suggests a method for therapeutic deletion. Plasma cells from mice prone to systemic lupus erythematosus did not express FcgammaRIIb and were protected from apoptosis. Human plasmablasts expressed FcgammaRIIb and were killed by crosslinking, as were FcgammaRIIb-expressing myeloma cells. Our results suggest that FcgammaRIIb controls bone marrow plasma cell persistence and that defects in it may contribute to autoantibody production.
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                Author and article information

                Journal
                World Allergy Organ J
                World Allergy Organ J
                wox
                The World Allergy Organization journal
                World Allergy Organization Journal
                1939-4551
                15 June 2010
                June 2010
                : 3
                : 6
                : 195-201
                Affiliations
                IPAP-Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria.
                Author notes
                Correspondence to: Erika Jensen-Jarolim, MD, Department of Pathophysiology and Allergy Research, Medical University of Vienna, AKH-EB03.Q, Wäehringer Gürtel 180, 1090 Vienna, Austria. Telephone: +43-1-40400-5120. Fax: +43-1-40400-5130. E-mail: erika.jensen-jarolim@ 123456meduniwien.ac.at .

                This work was supported by the SFB grant F1808-B13 and the Hertha Firnberg stipend T283-B13, both of the Austrian Science Fund (FWF).

                Article
                10.1097/WOX.0b013e3181e61ebf
                2999829
                21151813
                e66aead7-0d31-436a-b3b1-094e5bcb98fb
                Copyright © 2010 by World Allergy Organization
                History
                Categories
                Basic and Clinical Translational Science in Allergy, Asthma and Immunology Review Series

                Immunology
                fcεri,anti-idiotypes,vaccination,fcγriib,allergy,blocking
                Immunology
                fcεri, anti-idiotypes, vaccination, fcγriib, allergy, blocking

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