Antibodies constant domains

The most remarkable feature of the antibody molecule is revealed by comparing the amino acid sequences from many different immunoglobulin IgG molecules. This comparison shows that between different IgGs the amino-terminal domain of each polypeptide chain is highly variable, whereas the remaining domains have constant sequences. A light chain is thus built up from one amino-terminal variable domain (Vl) and one carboxy-terminal constant domain (Cl), and a heavy chain from one amino-terminal variable domain (Vh), followed by three constant domains (Chi, Ch2. and Chs). 

IgG antibody molecules are composed of two light chains and two heavy chains joined together by disulfide bonds. Each light chain has one variable domain and one constant domain, while each heavy chain has one variable and three constant domains. All of the domains have a similar three-dimensional structure known as the immunoglobulin fold. The Fc stem of the molecule is formed by constant domains from each of the heavy chains, while two Fab arms are formed by constant and variable domains from both heavy and light chains. The hinge region between the stem and the arms is flexible and allows the arms to move relative to each other and to the stem. 

Antibody classes In mammals, there are five classes of antibodies (also known as immunoglobulins IgG, IgA, IgM, IgE and IgD). Each immunoglobulin class differs in their heavy chain constant domains (see Fig. 1.2) and consequently in its biological properties. For immunoassays, two immuno-glubulin classes are of importance - IgG and IgM. 

Figure 1.10. Generalised structure of the variable and constant domains within antibodies. The variable regions (dark shading) of either the light or heavy chains are indicated as VL or VH, respectively. The light chains also possess one constant region (CL), whereas the heavy chains possess either three or four constant regions (Ch)-Ch4). depending upon the class of immunoglobulin (see text for details).

IgA has a short half-life in serum (6 days) and comprises about 12-20% of the total serum immunoglobulins. However, because of its presence in bodily fluids, it is the most abundant immunoglobulin present in the body. It comprises three constant domains, and neutrophils, monocytes and some other immune cells possess receptors for IgA (FcaR). Neither of the two IgA subclasses, IgAi and IgA2, can fix complement via the classical pathway. Instead, these antibodies neutralise antigens at mucosal surfaces, in the absence of complement fixation (which would be pro-inflammatory), and the neutralised antigens are cleared. 

Fig. 6.1. Rendition of an IgG antibody molecule and its interaction sites. V, variable regions L, light chain VH1 and CH 1-4, constant domains of the heavy chain. Sites of C1q, FcgR, and FcRn binding are indicated.

Antibody with specificity for APC, which has an antigenic sequence inserted into a constant domain region. See Lunde, E., Lauvrak, V., Rasmussen,... 

Ubol, S., Levine, B., Lee, S. H., Greenspan, N. S., and GrifSn, D. E. (1995). Roles of immunoglobulin valency and the heavy-chain constant domain in antibody-mediated downregulation of Sindbis virus replication in persistently infected neurons./ Virol. 69, 1990-1993. 

Chapman and Liljas, Fig. 3. The immunoglobulin fold, (a) The constant domain of the light chain of an antibody (b) the immunoglobulin domain of tick-bome encephalitis glycoprotein E (Rey et oL, 1995). 

Figure 33.8. Variable and Constant Regions. Each L and H chain includes one immunoglobulin domain at its amino terminus that is quite variable from one antibody to another. These domains are referred to as Vl and Vfj. The remaining domains are more constant from one antibody to another and are referred to as constant domains (ClI, Ch2, and Ch3).

---