Structural Features of Antibody Constant Regions

Antibody molecules can be divided into distinct classes and subclasses on the basis of differences in the structure of their heavy chain C regions. The classes of antibody molecules are also called isotypes and are named IgA, IgD, IgE, IgG, and IgM (Table 5-2). In humans, IgA and IgG isotypes can be further subdivided into closely related subclasses, or subtypes, called IgA1 and IgA2 and IgG1, IgG2, IgG3, and IgG4. (Mice, which are often used in the study of immune responses, differ in that the IgG isotype is divided into the IgG1, IgG2a, IgG2b, and IgG3 subclasses; certain strains of mice, including C57BL/6, lack the gene for IgG2a but synthesize a related isotype called IgG2c). The heavy chain C regions of all antibody molecules of one isotype or subtype have essentially the same amino acid sequence. This sequence is different in antibodies of other isotypes or subtypes. Heavy chains are designated by the letter of the Greek alphabet corresponding to the isotype of the antibody: IgA1 contains a1 heavy chains; IgA2, a2; IgD, 8; IgE, e; IgG1, y1;

Antigen

Antigen moM

Antigen

FIGURE 5-6 Binding of an antigen by an antibody. A, A schematic view of complementarity-determining regions (CDRs) generating an antigen-binding site. CDRs from the heavy chain and the light chain are loops that protrude from the surface of the two Ig V domains and in combination create an antigen-binding surface. B, This model of a globular protein antigen (hen egg lysozyme) bound to an antibody molecule shows how the antigen-binding site can accommodate soluble macromolecules in their native (folded) conformation. The heavy chains of the antibody are red, the light chains are yellow, and the antigen is blue. (Courtesy of Dr. Dan Vaughn, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.) C, A view of the interacting surfaces of hen egg lysozyme (in green) and a Fab fragment of a monoclonal anti-hen egg lysozyme antibody (VH in blue and VL in yellow) is provided. The residues of hen egg lysozyme and of the Fab fragment that interact with one another are shown in red. A critical glutamine residue on lysozyme (in magenta) fits into a "cleft" in the antibody. (Reprinted with permission from Amit AG, RA Mariuzza, SE Phillips, and RJ Poljak. Three dimensional structure of an antigen antibody complex at 2.8A resolution. Science 233, 747-753, 1986. Copyright 1986 AAAS.)

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