For most practical purposes, an epitope is easy to define as that part of an antigen involved in its recognition by an antibody (or, in the case of T-cell epitopes, by a T-cell receptor). Although simple chemical molecules, nucleic acids, and carbohydrates can all act as antigens, the term “epitope mapping” is usually applied to protein antigens, and is the process of locating the epitope on the protein surface or in the protein sequence. The simplicity is deceptive, however, and conceptual problems soon make their practical consequences felt. A considerable understanding of the principles of protein structure and protein folding, and some knowledge of the nature of the immune response may quickly become necessary for the correct interpretation of experimental epitope mapping results. The term “epitope mapping” has also been used to describe the attempt to determine all the major sites on a protein surface that can elicit an antibody response, at the end of which one might claim to have produced an “epitope map” of the protein antigen (1). This information might be very useful, for example, to someone wishing to produce antiviral vaccines. Implicit in this view of epitopes is that they are fixed and concrete structures on protein surfaces, which are few in number and uniquely capable of stimulating the immune system. Even if this is true for proteins in their native conformation, it is a limitation imposed by protein structure rather than the immune system, since additional immunogenic determinants are readily revealed by protein unfolding. This kind of “epitope map” also confuses the important distinction between antigenicity (the ability to recognize a specific antibody) and immunogenicity (the ability to produce antibodies in a given animal species). Most people would agree that epitopes should be defined by their antigenicity.
KeywordsAntibody Binding Phage Display Peptide Library Individual Amino Acid Epitope Mapping
- 4.Barlow, D. J., Edwards, M. S., and Thornton, J. M. (1986) Continuous and discontinuous protein antigenic determinants. Nature 322, 747–748.Google Scholar
- 6.Greenspan, N. S. (1992) Epitopes, paratopes and other topes: do immunologists know what they are talking about? Bull. Inst. Pasteur 90, 267–279.Google Scholar
- 10.Stanley, K. K. (1988) Epitope mapping using pEX. Methods Mol. Biol. 4, 351–361.Google Scholar