MIMOTOPES, CONTINUOUS PARATOPES AND HYDROPATHIC COMPLEMENTARITY - NOVEL APPROXIMATIONS IN THE DESCRIPTION OF IMMUNOCHEMICAL SPECIFICITY

Most antigenic sites of proteins, known as discontinuous epitopes, are made up of residues on different loops that are brought together by t he folding of the polypeptide chain. The individual loops are sometime s able, on their own, to bind to the antibody and they are then known as continuous epitopes. The binding sites of antibodies, known as para topes, are built up from residues on six hypervariable loops known as complementarity determining regions (CDRs). Peptides corresponding to individual CDR loops are often able to bind the antigen and such pepti des may be viewed as continuous paratopes. Using random combinatorial peptide libraries, it is possible to obtain peptides that bind to an a ntiprotein antibody without showing any sequence similarity with any p art of the protein. Such epitope mimics are called mimotopes provided they are able also to elicit antibodies that react with the original a ntigen. The binding activity of mimotopes may partly be due to the phe nomenon of hydropathic complementarity between epitope and paratope pe ptides. Although these concepts are vague in their structural connotat ion, they are useful for describing the immunological activity of line ar peptides.