tural configuration in the respective molecules. If a closely-related molecule has an additional conformational change, even moving a prosthetic group from a para-to a meta-position (Fig. 1), then that close fit is greatly compromised and there is either no reaction or a very much weaker one.
The availability of myeloma immunoglobulins, for which antigenic reactivity is known, afforded the immunochemist with a homogenous population of antibodies whose light and heavy chain variable domains could be sequenced. Now the exact molecular structure of the antibody as well as the antigen could be known. The amino acid sequence of a polypeptide determines how that peptide will fold three-dimensionally in space and that degree of folding is the antibody characteristic which allows the complementary fit of its homologous antigen. Fig. 3 shows the key amino acids in light and heavy chains that are in most intimate contact with a phosphorylcholine hapten. Essentially, the antigen fits in a very tight cleft formed by the folding of the light and heavy immunoglobulin chains. The lock-and-key analogy used for so many decades to explaining antigen-antibody fit has proven to be remarkably accurate.