The notion of an “antibody” goes back to Paul Ehrlich, who coined the German term antikoper in 1891. He proposed the idea of a lock-and-key mechanism for the binding of antibody to antigen. However, no-one really understood how a set of rather identical looking antibodies could recognise thousands or even millions of different antigens. The answer lay in the three-dimensional structure of the antibody, revealed independently by Gerald Edelman at Rockefeller University in New York and Rodney Porter of Oxford University.
The antibody posed a great problem in terms of studies into structure and function. It was just too big to handle. Edelman and Porter tried to deconstruct the problem by cutting the antibody down to size. Edelman did it by using chemicals to break the bridge-like sulphur bonds that keep the constituent protein chains together, while Porter used a protein-cleaving enzyme that fragmented an antibody molecule into its functional subsections.
The outcome was that the two scientists’ studies taken together demonstrated that antibodies are composed of two long, heavy protein chains and two identical shorter, light chains. They combine to form the three sections of a “Y” shaped giant molecule. At both arms of the “Y”, a light chain is paired up with a heavy chain to form the unique binding site for each specific target. The antigen in other words sits in the form of the Y.
A third section links the two heavy chains together to form the stem of the “Y”. It is this stem section that doesn’t change significantly from one antibody to another, and takes on the role of binding to other key components of the immune system to mount a defence against an invasive pathogen.
The beauty of this Y-shape molecule is that although the basic structure remains the same, millions of slight variations can be produced by changing the sequence of amino acids in the protein strands at the ends of the two arms of the “Y” molecule. It is that variation in structure that allows the immense variation in antibody specificity.
Edelman and Porter had laid the foundation for truly rational research into the structure and function of a key component of the immune system, for which they shared equally in the 1972 Nobel Prize in Physiology or Medicine.