Fc Receptor Phagocytosis

CHAPTER 3

Fc Receptor Phagocytosis Randall G. Worth and Alan D. Schreiber

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ntigen recognition by cells of the immune system occurs via many mechanisms. One important family of receptors involved in the recognition of immunoglobulin (Ig) coated particles and complexes are Fc receptors. Fc receptors recognize the Fc portion of Ig and are accordingly grouped into subfamilies. They are named depending upon which class of Ig they bind. The major Fc receptors are Fey receptors which bind IgG, FcaR that bind IgA and FceR bind IgE.^' Fc receptors are responsible for such functions as endocytosis,^'^ phagocytosis, granule release, ^ reactive mediator release and cell activation/cytotoxicity. Fc receptors are found on specific cell types corresponding to their ability to recognize Ig. For example, FcE receptors are found primarily on eosinophils, basophils and mast cells where they trigger histamine release from intracellular granules whereas Fey receptors are found primarily on neutrophils, macrophages and monocytes where they can detect and phagocytose IgG coated pathogens.^ '^^

Fc Receptor Structure Fc receptors can be divided into two groups based on their signaling capabilities and structure. The first and most common type of Fc receptor is a multi-chain heterocomplex composed of a ligand binding a-chain and one or more signal transducing y-chains. The second type of Fc receptor is a single-chain transmembrane receptor containing a signal generating motif(s) in the cytoplasmic domain and, thus, not requiring another signal transducing subunit. In this presentation, the Fey receptor family will be discussed as a model system in phagocytic signaling. Fc receptors for a specific isotype of Ig can vary in structure and can differ in ligand affinity and signaling ability (reviewed in Ravetch and Holland)."^ Fey receptors are classified into three classes: FcyRI, FcyRII, and FcyRIIL FcyRI is a high affinity receptor that can be subdivided into three groups (A, B and C) that are encoded by three different genes. Similar to FcyRI, FcyRII has been divided into three families encoded by three genes, also named A, B and C and which are of relatively low affinity for monomeric IgG but of high affinity for complexed IgG. FcyRIIB is expressed in two forms following alternative splicing, forming the FcyRIIB 1 and FcyRIIB2 isoforms. FcyRIII is divided into two families, the transmembrane form FcyRIIIA and the glycosylphosphatidylinositol (GPI) linked FcyRIIIB. There are several forms of each of these receptors based on their glycosylation patterns.^^''^ Given that most Fey receptors are transmembrane proteins, the first step of receptor activation and subsequent phagocytosis is binding of IgG containing complexes to the receptor extracellular domain. This crosslinking has been observed to induce Fey receptors to preferentially localize into lipid rafts."^"^'^^ The partitioning into lipid rafts may aid in recruiting and complexing with additional signaling proteins associated with lipid rafts.^^'^'^ Molecular Mechanisms of Phagocytosis^ edited by Carlos Rosales. ©2005 Eurekah.com and Springer Science+Business Media.

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Molecular Mechanisms ofPhagocytosis

Table 1. Size and affinity for ligand of common Fof receptors

Molecular Mass IgG Specificity IgG Affinity

FcyRI

FcyRrrA

FcyRIIB

FcyRIII

70kDa 1>=3>4>2 10-7-10-^M

40kDa 3>1>2>4

40kDa 3>=1>4>2

50-80 kDa 1=3>2=4