Studies on the Structure and Formation of Antibodies

Abstract

When we began to work on antibodies in 1929, we found soon that the nonantigen portion of the antigen-antibody precipitate had a composition similar to that of the serum globulins and that it was free of any non-protein prosthetic group. We drew the following conclusions: (1) the globulin found in the antigen-antibody precipitates is indeed antibody and not a contaminant of antibody molecules of unknown composition as suspected by many scientists at that time; (2) the formation of the antigen-antibody complex is caused by a close complementary fit between the peptide chains of the antibody molecule and the determinant groups of the antigen; and finally, (3) the complementary fit of the antibody molecule might be accomplished by interference of the administered antigen with the biosynthesis of the antibody globulins and with changes in the amino acid composition of the antibody molecules. According to this view the antigen acted as a template which instructed the cell what antibody it has to form. While conclusions (1) and (2) have been confirmed and are now widely accepted, the template hypothesis is at present less attractive than other views on the role of the antigen, although some instructive action of the antigen cannot yet be excluded. The principal reason for this change in our views is the enormous heterogeneity of the immunoglobulin population. Each of us may indeed have many thousands if not millions of different immunoglobulin molecules. Their number may be so high, that almost any injected antigen may encounter a molecule complementarily adapted to the antigenic determinants. The great heterogeneity of the immunoglobulin population has prevented complete elucidation of their amino acid sequence and has also made difficult the elucidation of the mechanism of antibody formation.