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An antigen is any object that, when injected into a vertebrate (animal), can stimulate the production of neutralizing antibodies. Immunoglobulins are antibodies. They are Y-shaped proteins, and they bind the antigen and neutralize its effect. This provides a defence against foreign proteins since it allows an organism to distinguish between its own molecules and foreign ones. Potentially immunogenic small molecules are called haptens. The immunoglobulin or antibody has two binding sites so that it can link similar antigens together to form an aggregate that can be destroyed by macrophages.
Each specific antibody possesses a unique sequence of amino acids (in the `recognition site'). These portions of the antibody fold in three dimensions in a unique way. The antigen causes the synthesis of the specific nucleotide sequence in an RNA template that codes for the desired amino acid sequence. All antibodies are composed of four chains, two light and two heavy and these are linked together by disulfide bonds. Both the light and heavy chain have variable sequences at their amino terminal end and constant regions at their carboxyl ends. The antigen combining sites (the `active' or `recognition' or `binding' sites) are formed by amino acids at the variable regions of both the light and heavy chains.
X-ray studies have given a wealth of information on the three-dimensional structures of the binding sites of two antibodies. The human immunoglobulin protein `New' that binds vitamin K, and a mouse immunoglobulin protein that binds phosphorylcholine have been studied. These show that residues forming the sites that are complementary to the antigen are contributed by the hypervariable regions (three segments of 5-10 residues each, in both chains). Replacement of amino acids in these areas give rise to binding sites with new specificities, but does not disturb the `immunoglobulin fold' (the general shape of the immunoglobin).
1. Intact human immunoglobulin. Silverton, E. W., Navia, N. A. and Davies, D. R., Proc. Natl. Acad. Sci. USA 74 (1977) 5140.
2. Fab fragment. Poljak, R. J., Amzel, L. M., Zvey, H. P., Chen, B. L., Phizackerly, R. P. and Saul, F., Proc. Natl. Acad. Sci. USA 70 (1973) 3305; Segal, D. M., Padlan, E. A., Cohen, G. H., Rudikoff, S., Potter, M. and Davies, D. R., Proc. Natl. Acad. Sci. USA 71 (1974) 4298: Padlan, E. A., Q. Rev. Biophys . 10 (1977) 35.
3. Fc fragment. Deisenhofer, J., Colman, P. M., Epp, O. and Huber, R., Z. Physiol . 357 (1976) 1421.
4. Immunoglobulin Kol and its antigen-binding fragment. Marquart, M., Deisenhofer, J., Huber, R. and Palm, W., J. Mol. Biol . 141 (1980) 369.
5. Combining region-ligand complex of immunoglobulin NEW at 3.5 Å resolution. Amzel, L. M., Poljak, R. J., Saul, F., Varga, J. M. and Richards, F. F., Proc. Natl. Acad. Sci. USA 71 (1974) 1427.
6. NMR studies using X-ray results. Dwek, R. A., Wain-Hobson, S., Dower, S., Gettins, P., Sutton, B., Perkins, S. J. and Givol, D., Nature 266 (1977) 31.
7. Allergy. Buisseret, Paul D., Scientific American , 247 (1982) 2.
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