The basic unit of an antibody structure is the homology unit, or domain. A typical molecule has 12 domains, arranged in two heavy (H) and two light (L) chains, linked through cysteine residues by disulfide bonds so that the domains lie in pairs (Fig. 1). The antigen-binding portion of the molecule (N-terminal end) shows such heterogeneity that it is known as the variable (V) region; the remainder is composed of relatively constant amino acid sequences, the constant (C) region. Short segments of about 10 amino acid residues within the variable regions of antibodies (or T cell receptor [TCR] proteins) form loop structures called complementary-determining regions (CDRs). Three hypervariable loops, also called CDRs, are present in each antibody H chain and L chain. Most of the variability among different antibodies or TCRs is located within these loops.

Fig1. Basic immunoglobulin configuration. (Adapted from Turgeon ML: Fundamentals of immunohematology, ed 2, Baltimore, 1995, Williams & Wilkins.)

The IgG molecule provides a classic model of antibody structure, appearing Y-shaped under electron microscopy (Fig. 2). If the molecule is studies by chemical treatment and the interchain disulfide bonds are broken, the molecule separates into four polypeptide chains. Light chains are small chains (25,000 Da) common to all Ig classes. The L chains are of two subtypes, kappa (κ) and lambda (λ), which have different amino acid sequences and are antigenically different. In humans, about 65% of Ig molecules have κ chains, whereas 35% have λ chains. The larger H chains (50,000 to 77,000 Da) extend the full length of the molecule.

Fig2. Basic structure of IgG. (Adapted from Turgeon ML: Fundamentals of immunohematology, ed 2, Baltimore, 1995, Williams & Wilkins.)

A general feature of the Ig chains is their amino acid sequence. The first 110 to 120 amino acids of both L and H chains have a variable sequence and form the V region; the remainder of the L chains represents the C region, with a simi lar amino acid sequence for each type and subtype. The remaining portion of the H chain is also constant for each type and has a hinge region. The class and subclass of an Ig molecule are determined by its H-chain type.