Components of an antibody and the genes that encode them

Both the L and H chains are composed of globular 'domains' connected by flexible segments with extended conformations, like cylindrical beads on a string (see Figures 1-5). An L chain has two domains - a V ('variable') unit with 108-111 amino acid residues, and a C ('constant') unit with about 105 residues (Figure 1). The variable domain is so named because its amino acid sequence differs from protein to protein, even within the same antigenic class and species. Within each isotype, the sequence of the constant domain changes very little (usually in four or fewer positions). Each V domain is encoded by two genes. The VL gene specifies the first 95 residues and the JL ('joining') gene dictates the remainder. Both the VL and JL gene products contribute to the antigen-binding site of the antibody (i.e. the CDRs, the 'complementarity-determining regions') and to the FRs ('framework regions') of the domain. The tail of the JL segment joins the first few residues of the CL domain to form the flexible 'switch' region bridging the V and C domains.

In an H chain, the V domain is composed ot the products of three genes: VH, D ('diversity') and Jn. VH encodes CDR1 and 2, as well as FR1, 2 and 3, and all three genes share responsibility for CDR3. JM specifies FR4 and part of the switch region. Three C domains (four in IgM and IgE molecules), each encoded by a single gene (CH1, Cn2, and C',,3), are connected to the VH domain in human antibodies.

In IgG proteins the repeating unit is the combination of one L and one H chain (L-H heterodimer), normally linked covalently by an interchain disulfide bond. VL and VH domains are paired via noncovalent interactions to form an Fv ('fragment, variable') region, at the tip of which is the binding site for antigen. Pairing interactions of the Q and CHI domains involve a different set of surfaces than those of the V domains (see section on 'The immunoglobulin fold', below). Together, these V and C pairs constitute the Fab ('fragment, antigen-binding') (Figure 2).

To produce the normal four-chain IgG structure, the H chains in two L-H heterodimers are held together covalently by at least one interchain disulfide bond and noncovalently by very tight interactions between the CH3 domains. The combination of the CH2 and CH3 domains from the two heavy chains is called the Fc ('fragment, crystalline'), since this unit tends to crystallize when released from an IgG molecule by the enzyme papain (Figure 3).

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