Laboratorio Clinico

Clinical and Experimental Immunology

R EV I EW ART I CLE

doi:10.1111/j.1365-2249.2010.04210.x

CD23/FceRII: molecular multi-tasking

cei_4210 12..23

M. Acharya,1* G. Borland,2* A. L. Edkins,3* L. M. MacLellan,4* J. Matheson, B. W. Ozanne† and W. Cushley*
*Division of Molecular and Cellular Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, and †CR-UK BeatsonInstitute, Glasgow, UK Accepted for publication 18 May 2010 Correspondence: W. Cushley, Division of Molecular and Cellular Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK. E-mail: w.cushley@bio.gla.ac.uk Present addresses: 1Laboratory of Pediatric Immunology, Department of Developmental Immunology, Massachusetts General Hospital, 55 FruitStreet, Boston, MA 02114, USA; 2 Molecular Oncology Laboratory, Institute of Comparative Medicine, University of Glasgow, Glasgow G61 1QH, UK; 3Biomedical Biotechnology Research Unit (BioBRU), Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6139, Republic of South Africa; 4Division of Clinical Neurosciences, Glasgow Biomedical Research Centre, University of Glasgow, GlasgowG12 8QQ, UK.

Summary CD23 is the low-affinity receptor for immunoglobulin (Ig)E and plays important roles in the regulation of IgE responses. CD23 can be cleaved from cell surfaces to yield a range of soluble CD23 (sCD23) proteins that have pleiotropic cytokine-like activities. The regions of CD23 responsible for interaction with many of its known ligands, including IgE, CD21, majorhistocompatibility complex (MHC) class II and integrins, have been identified and help to explain the structure–function relationships within the CD23 protein. Translational studies of CD23 underline its credibility as a target for therapeutic intervention strategies and illustrate its involvement in mediating therapeutic effects of antibodies directed at other targets. Keywords: CD23, cytokines, IgE,immunoregulation, integrins

Introduction
Immune responses are subject to regulation at many levels, including the influence of different groups of cytokines, cell– cell contact via adhesion interactions and receptor-mediated positive and negative feedback circuits. The low-affinity receptor for immunoglobulin (Ig)E, also known as FceRII or CD23, participates in all these regulatory processes, either as amembrane-bound glycoprotein or as a freely soluble protein. Structural biology approaches have revealed the fine molecular details of the soluble CD23 (sCD23) protein and the interaction surfaces used by sCD23 to bind its various ligands, and molecular biological and mutagenesis studies have defined critical residues involved in performance of
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biological functions. CD23 has been suggested tohave utility as a diagnostic marker in a range of diseases and to be implicated in the cellular and molecular processes associated with a variety of pathological states; the latter feature has made CD23 a target for therapeutic intervention.

General features of CD23
CD23 was defined initially as the low-affinity receptor for IgE [1,2]. As a membrane protein, CD23 is a type II transmembraneglycoprotein of approximately 45 kDa molecular weight comprising a large C-terminal globular extracellular domain that is strikingly similar to C-type lectins, followed by a stalk region bearing several repeats that serve as a

© 2010 The Authors Clinical and Experimental Immunology © 2010 British Society for Immunology, Clinical and Experimental Immunology, 162: 12–23

Immunobiology of CD23Fig. 1. Primary structural features of human CD23. (a) The 321 amino acids that comprise the primary structure of human CD23a [1,2,55]. Individual contact residues or binding regions for CD23 ligands are shown in green (major histocompatibility complex class II [45]), bold type (av integrins [51]), blue (IgE [44]) or red (CD21 [44]). The colours of the latter three interaction surfaces are...