The Interaction of Antibodies with Antigens

Antibodies are proteins synthesized and secreted by B cells that bind to antigens. Most antigens aremacromolecules: proteins, polysaccharides, even DNA and RNA.

The interaction occurs: by noncovalent forces (like that between enzymes and their substrate) between the antigen-combining site on the antibody and a portion of the antigen called the antigenic determinant or epitope.

These photos show one type of interaction — precipitation — between antibodies and antigen.
(a) The tube contains antibodies to the Type III pneumococcal polysaccharide isolated from the capsule surrounding the bacteria.
(b) A solution of the polysaccharide is added, and
(c) the formation of insoluble antigen-antibody complexes is revealed by the almost instantaneous appearance of turbidity.
(d) After an hour, the complexes settle out as a precipitate. If the proportion of antigen to antibody in the mixture is selected properly, the fluid above the precipitate will be devoid of both.
In the human body, this binding can literally be life-saving.

The capsule that surrounds pneumococci protects them from phagocytosis. (Pneumococci that fail to make a capsule — "R" forms — do not cause disease.

If the appropriate antibodies are present in the body, they combine with the capsule. Coated with protein instead of polysaccharide, the pneumococci are now easy to ingest.

These photomicrographs show phagocytosis of antibody-coated pneumococci.

Left: A neutrophil extends a pseudopod toward two pneumococci.
Center: these bacteria have been engulfed (arrows), and the neutrophil is beginning to engulf four more pneumococci at the upper right.
Right: Two pneumococci have escaped.
(From W. B. Wood, M. R. Smith, and B. Watson, Journal of Experimental Medicine 84:387, 1946.)

In the days before antibiotics, the start of antibody production by the immune system of the patient marked the turning point in the progression of the disease.
 

The Antigen-Combining Site

The diagram on the top shows the primary structure of an IgG antibody. Different IgG antibodies differ most markedly at the so-called hypervariable regions (shown in red): three in the heavy chain and three in the light chain In the three-dimensional (tertiary) structure of the molecule, the 6 hypervariable regions are brought close together and make up the antigen-combining site.

Marked are the constant region of the light chain (CL) and the first constant region of the heavy chain(CH); variable regions of the heavy (VH) and light chains (VL);
the third hypervariable region of the heavy (Hv3H) and light (Hv3L) chains. Gln121 is a glutamine that is a dominant feature of the epitope on lysozyme.

The second image is a space-filling model of the same antibody with the light chain in yellow, the heavy chain in blue. The view is looking down on the epitope-binding surface (left) and the epitope on lysozyme (right). In the antigen-antibody complex, the two surfaces fit snugly together. The 17 amino acid residues that contact lysozyme in the antigen-antibody complex are numbered (1–7 on the L chain, 8–17 on the H chain. The 16 amino acid residues of lysozyme that contact the antibody; that is, that make up its epitope are also numbered. Number 14 is Gln-121.

The complementarity of the antigen-binding site and the epitope, i.e., their respective shapes and the opportunities for multiple noncovalent interactionsdetermine how strongly the two bind together.

The strength of the binding of an antibody to its antigen is called its affinity. Affinity is discussed in a separate page.

The IMMUNOLOGY ^® 2005 Md. Abraham LICHTMAN