Introduction

Antibodies are multifunctional protein molecules capable not only of recognizing and binding to foreign antigens but also activating a range of molecular and cellular responses in the host that lead to neutralization or destruction of the invading organism or foreign material. Antibodies, or immunoglobulins, are built upon a common four-chain structure of two heavy and two light chains, as exemplified by immunoglobulin G (IgG) (Fig. 1A), each chain consisting of a tandem array of domains. Antigen binding occurs at the V (variable) domains, which determine the specificity of the antibody for antigen, but the C (constant) domains of the heavy chain (in the Fc region; Fig. 1A) are responsible for the subsequent effector functions of the antibody.

The five classes of antibody (IgA, IgD, IgE, IgG, and IgM) are distinguished by the C domain sequences of their heavy chains (a, 5, e, y, and |J.), each with a distinct range of effector functions and a specialized role in the body's immune system. Many of the cell-surface receptors for the Fc regions of these antibodies have been identified, but here we shall be concerned only with those for which the three-dimensional structures and their complexes with the antibody Fc are known, namely IgG- and IgE-receptor interactions. IgE, the antibody responsible for antiparasitic responses but nowadays better known for its association with allergic disease, differs from IgG, the principal serum antibody responsible for the secondary immune response to infection, in having an additional pair of domains in its

Fc region in place of the flexible hinge region of IgG (Fig. 1B). The Fc regions of IgA and IgM, which can form dimers and pentamers, respectively, of the basic four-chain unit (and are stabilized by additional polypeptide chains), are more complex still, but the three-dimensional structures of these uncomplexed antibody Fc regions are still unknown.

To date, structural information is available for three distinct types of cell-surface Fc receptors. The first of these is the family consisting of the IgG Fc receptors, FcyRI, II (a and b), and III (a and b), as well as the IgE receptor FceRI and IgA receptor FcaRI. All consist of an a-chain with two (three for FcyRI) extracellular, Ig-like, ligand-binding domains, either alone (FcyRIIa and b, IIIb) or associated with p and/or a pair of y-chains (FcyRI, IIIa, FceRI and FcaRI). (For reviews, see references [1-4].) The single-chain FcyRIIIb and four-chain FceRI (the two for which crystal structures of their extracellular domains complexed with Fc are known) are shown schematically in Figs. 1C and D. Distinct from this family of receptors, however, are the neonatal IgG Fc receptor, FcRn, which is responsible for the transport of IgG across the placenta, and the low-affinity receptor for IgE, FceRII (or CD23), which is involved in both allergen uptake by antigen-presenting cells and regulation of IgE synthesis by B cells. Whereas FcRn belongs to the class I major histocompatibility complex (MHC) family (Fig. 1E) [5], FceRII is a trimeric C-type lectin with a wholly different molecular architecture and oligomeric structure (Fig. 1F) [6]. The nature of the interactions between these three different types of receptor and

Handbook of Cell Signaling, Volume 1

Cy1:CL\

Fourni CD23

FouRi

FcyRlllb

Figure 1 Schematic representations, drawn to scale, of the domain structures of: (A) IgG; (B) IgE; (C) GPI-anchored, low-affinity IgG receptor FcyRIIIb; (D) high-affinity IgE receptor FceRI; (E) neonatal IgG receptor FcRn; and (F) low-affinity IgE receptor FceRII (CD23). Molecules A through D consist of Ig or Ig-like domains, FcRn is class I MHC-like, and FceRII consists of C-type lectin domains linked to the membrane and trimerised through an a-helical coiled-coil stalk.

Fourni CD23

FouRi

FcyRlllb

Figure 1 Schematic representations, drawn to scale, of the domain structures of: (A) IgG; (B) IgE; (C) GPI-anchored, low-affinity IgG receptor FcyRIIIb; (D) high-affinity IgE receptor FceRI; (E) neonatal IgG receptor FcRn; and (F) low-affinity IgE receptor FceRII (CD23). Molecules A through D consist of Ig or Ig-like domains, FcRn is class I MHC-like, and FceRII consists of C-type lectin domains linked to the membrane and trimerised through an a-helical coiled-coil stalk.

Fc will be discussed first for the IgG and then for the IgE receptors.

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book


Post a comment