immunoglobulin polypeptide. This region, called the variable (V) domain, is composed of amino acid sequences that define each type of antibody and their binding affinity to an antigen. The combined sequence of variable light chain (VL) and variable heavy chain (VH) creates three hypervariable regions (HV1, HV2, and HV3). In VL these are roughly from residues 28 to 35, from 49 to 59, and from 92 to 103, respectively. HV3 is the most variable part. Thus these regions may be part of a paratope, the part of an antibody that recognizes and binds to an antigen. The rest of the V region between the hypervariable regions are called framework regions. Each V domain has four framework domains, namely FR1, FR2, FR3, and FR4. Properties Chemical basis of antigen-antibody interaction Antibodies bind antigens through weak chemical interactions, and bonding is essentially non-covalent. Electrostatic interactions, hydrogen bonds, van der Waals forces, and hydrophobic interactions are all known to be involved depending on the interaction sites. Non-covalent bonds between antibody and antigen can also be mediated by interfacial water molecules. Such indirect bonds can contribute to the phenomenon of cross-reactivity, i.e. the recognition of different but related antigens by a single antibody. Affinity of the interaction Antigen and antibody interact through a high affinity binding much like lock and key. A dynamic equilibrium exists for the binding. For example, the reaction is a reversible one, and can be expressed as: [Ab] + [Ag] <=> [AbAg] where [Ab] is the antibody concentration and [Ag] is the antigen concentration, either in free ([Ab],[Ag]) or bound ([AbAg]) state. The equilibrium association constant can therefore be represented as: where K is the equilibrium constant. Reciprocally the dissociation constant will be: However, these equations are applicable only to a single epitope binding, i.e. one antigen on one antibody. Since the antibody necessarily has two paratopes, and in many circumstances complex binding occurs, the multiple binding equilibrium can be summed up as: where, at equilibrium, c is the concentration of free ligand, r represents the ratio of the concentration of bound ligand to total antibody concentration and n is the maximum number of binding sites per antibody molecule (the antibody valence). The overall strength of the binding of an antibody to an antigen is termed its avidity for that antigen. Since antibodies are bivalent or polyvalent, this is the sum of the strengths of individual antibody-antigen interactions. The strength