title: Comparative binding of soluble fragments (derCD23, sCD23, and exCD23) of recombinant human CD23 to CD21 (SCR 1-2) and native IgE, and their effect on IgE regulation.
abstract: IgE, responsible for type I hypersensitivities, is regulated by interactions between its receptor, CD23, and co-receptor CD21. To examine comparative binding of recombinant human CD21 SCR 1-2 and native human IgE to CD23 plus the effect of CD23 on IgE production, we engineered recombinant soluble human CD23 fragments; (1) derCD23, (2) sCD23 and (3) exCD23, formed in vivo by proteolysis. SPR analysis revealed a progressive increment in affinity of soluble fragments for IgE, upon increasing length of CD23 "stalk" domain, exCD23>sCD23>derCD23. Soluble CD23 fragments and their oligomeric state are shown to fine-tune the immune response. Oligomers appear more important in enhancing IgE synthesis and monomers lacking the tail residues fail to bind CD21 yet bind membrane IgE and down-regulate IgE synthesis. Co-ligation of membrane IgE and CD21 through soluble CD23 monomers is disturbed. This study supports anti-allergic therapies involving stabilizing membrane CD23, or preventing shedding of soluble CD23.
authors: Nelson Mandela Metropolitan University, Port Elizabeth, South Africa.
authors: Sandra Lyn
authors: SL
authors: Bowles
authors: Christiane
authors: C
authors: Jaeger
authors: Claudia
authors: C
authors: Ferrara
authors: Joyce
authors: J
authors: Fingeroth
authors: Maryna
authors: M
authors: Van De Venter
authors: Vaughan
authors: V
authors: Oosthuizen
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017464:Receptors, Complement 3d / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017455:Receptors, IgE / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012995:Solubility; D020349:Surface Plasmon Resonance; D055815:Young Adult
chemical_list: D010446:Peptide Fragments; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D011994:Recombinant Proteins; D007073:Immunoglobulin E