A typical monomeric IgG molecule consists of three globular regions (two Fab regions and an Fc portion) linked by a flexible hinge region. If the molecule is digested with a proteolytic enzyme such as papain, it splits into three approximately equal sized fragments (Fig. 1). Two of these fragments retain the ability to bind antigen and are called the antigen-binding fragments (Fab fragments). The third fragment, which is relatively homogeneous and is sometimes crystallizable, is called the Fc portion. If IgG is treated with another proteolytic enzyme, pepsin, the molecule separates somewhat differently. The Fc fragment is split into tiny peptides and thus is completely destroyed. The two Fab fragments remain joined to produce a fragment called F(ab)′2. This fragment possesses two antigen binding sites. If F(ab)′2 is treated to reduce its disulfide bonds, it breaks into two Fab fragments, each of which has only one antigen-binding site. Further disruption of the interchain disulfide bonds in the Fab fragments shows that each contains a light chain and half of a heavy chain, which is called the Fd fragment.

fig1. Enzymatic cleavage of human IgG1. (Adapted from Tur geon ML: Fundamentals of immunohematology, ed 2, 1995, Williams & Wilkins.)

Electron microscopy studies of IgG have revealed that the Fab regions of the molecule are mobile and can swing freely around the center of the molecule as if it were hinged. This hinge consists of a group of about 15 amino acids located between the C_H1 and C_H2 regions. The exact sequence of amino acids in the hinge is variable and unique for each Ig class and subclass. Because amino acids can rotate freely around peptide bonds, the effect of closely spaced proline amino acid residues is production of a so-called universal joint, around which the Ig chains can swing freely. A remarkable feature of the hinge region is the presence of a large number of hydrophilic and proline residues. The hydrophilic residues tend to open up this region and thus make it accessible to proteolytic cleavage with enzymes such as pepsin and papain. This region also contains all the interchain disulfide bonds except for IgD, which has no interchain links.