Identifying Heavy and Light Chains in Antibody Structures
With the help of gamma globulins and Bence-Jones proteins*, as well as various degrading, non-enzymatic compounds, Edelman was able to identify two independent amino acid chains, one with a molecular weight of 50-60 kDa and the other of 20-24 kDa. Each of these chains would later be denoted as the heavy (H) and light (L) chains of antibodies, respectively. Edelman would then go on to establish the bivalent nature of antibodies, consisting of two identical halves (each consisting of one H and one L chain) held together by disulfide bridges formed between cysteine residues. Edelman also hypothesized that parts of both the H and L chains contributed to the antibody’s antigen binding region.
Porter used a complementary, enzyme-based approach to arrive at similar conclusions. Armed with the papaya’s digestive enzyme papain, Porter was able to snip rabbit antibodies into three fragments, two of which were identical. The distinct fragments would become known as the antigen-binding fragment (Fab) and the crystallizable or constant fragment (Fc). Porter also noted that the Fab fragment consisted of both a H and L chain, thus confirming Edelman’s discoveries.
Porter and Edelman were awarded the 1972 Nobel Prize in physiology for their contributions to the field of immunology. In providing a clear picture of the basic structure of antibodies, their discoveries launched decades of structure and function research defining the antigen-binding complementarity-determining regions (CDRs) within the Fab and the diverse effector functions mediated by different Fcs.
*Bence-Jones proteins are antibody light chain dimers characteristically found in the urine of patients suffering from multiple myeloma, a cancer of antibody-producing plasma cells.