Much of our immune defense against invading organisms is predicated upon the tremendous diversity of immunoglobulin (Ig) molecules. Igs are glycoproteins produced by B lymphocytes and plasma cells. These molecules can be considered receptors because the primary function of the Ig molecule is to bind antigen. A single person can synthesize 10–100 million different Ig molecules, each having a distinct antigen-binding specificity. The great diversity in this so-called humoral immune system allows us to generate antibodies specific for a variety of substances, including synthetic molecules not naturally present in our environment. Despite the diversity in the specificities of antibody molecules, the binding of antibody to antigen initiates a limited series of biologically important effector functions, such as complement activation or adherence of the immune complex to receptors on leukocytes. The eventual outcome is the clearance and degradation of the foreign substance. This chapter describes the structure of Igs and outlines the mechanisms by which B cells produce molecules of such tremendous diversity with defined effector functions.
IMMUNOGLOBULIN STRUCTURE AND FUNCTION
All naturally occurring immunoglobulin (Ig) molecules are composed of one or several basic units consisting of two identical heavy (H) chains and two identical light (L) chains (Fig. 75–1).1 The four polypeptides are held in a symmetrical, Y-shaped structure by disulfide bonds and noncovalent interactions.2–4 The internal disulfide bonds of the H and L chains cause the polypeptides to fold into compact globe-shaped regions called domains, each containing approximately 110–120 amino acid residues. Each domain is composed of β-pleated sheets that are stabilized by a conserved disulfide bond (Fig. 75–1). The light chains have two domains; the heavy chains have four or five domains. The aminoterminal domains of the heavy and light chains are designated the variable (V) regions because their primary structure varies markedly among different Ig molecules. The carboxy-terminal domains are referred to as constant (C) regions because their primary structure is the same among Igs of the same class or subclass. The amino acids in the L- and H-chain V regions interact to form an antigen-binding site. Each four-chain Ig basic unit has two identical binding sites. The C-region domains of the H and L chains provide stability for the Ig molecule. The H-chain C regions also mediate the specific effector functions of the different Ig classes (Table 75–1).
Model of an immunoglobulin (Ig) G molecule. The light-chain domains VL and CL and the heavy-chain domains VH, Cγ1(or CH1), Cγ2 (or CH2), and Cγ3 (or CH3) are labeled inside the respective Ig domain. Dotted red colored lines indicate intrachain and interchain disulfide bonds. The aminoterminus (N) and carboxyl-terminus (C) of each polypeptide are indicated. The hinge region also is indicated. Digestion by pepsin cleaves the molecule at the carboxyl side of the hinge ...