Problems in Understanding the Generation of Antibody Complementarity

Abstract

A major problem of the present decade is the elucidation of the structural basis of antibody complementarity, or, in other words, what do antibody combining sites of a given specificity look like and how do the various amino acid side chains make for different kinds of combining sites (1–3). Intimately related to this is the question of how the capacity to make these sites is maintained in the germ line. The genetic basis for the formation of antibody combining sites differs from that of all other proteins with specific receptor sites such as enzymes, hormones and lectins in that antibody combining sites are formed by two chains whereas other receptor sites are essentially built of a single chain. It was generally estimated that mammals could form about 10⁶ antibody combining sites but since the development of the hybridoma technique (4) this estimate must clearly be low by several orders of magnitude since to date no two hybridomas making antibody combining sites to a single antigenic determinant such as αl→6 dextran have been found to be identical (5–7).