Antigenicity and Immunogenicity of Synthetic Peptides

The ability of a peptide to react specifically with the functional binding site of a complementary antibody is known as its antigenic reactivity or antigenicity. Our understanding of peptide antigenicity has improved considerably in recent years mainly through the X-ray crystallographic analysis of peptide-monoclonal antibody complexes. This knowledge is obtained along reductionist lines by turning the biological question of antigen recognition into the purely chemical phenomenon of protein-peptide interactions described in terms of atomic forces and non-covalent bonds. This makes it possible to improve the degree of steric complementarity between a peptide and a single monoclonal antibody and thus to improve the peptide's antigenicity following structure-based rational design principles.The situation is quite different with immunogenicity which is the ability of the peptide to induce an immune response in a competent host. Whereas antigenicity can be reduced to the level of chemistry, such a reduction is not achievable in the case of immunogenicity which depends on many complex interactions with various elements of the host immune system. These cellular and regulatory mechanisms cannot be controlled by adjusting the structure of the peptide in a predetermined manner. For this reason, it is not possible to develop a synthetic peptide vaccine using molecular design principles.