Antigen Recognition: 100 Years After Landsteiner

Abstract

A central feature of the adaptive immune system is its capacity to distinguish among an immense number of different structures. The efforts made over the past century to understand this extraordinary ability grew largely from Landsteiner’s work on the reactions of antisera with the small organic molecules he called haptens, or partial antigens, to indicate that they could react specifically with antibodies but not elicit antibody production. It was only near the end of his long, productive life that it became clear (through the work of Heidelberger and colleagues with polysaccharide antigens) that antibodies are proteins. And it was not until a fewyears after his death in 1943 that proteins were shown, by Fred Sanger, to be authentic molecules (rather than colloids) composed of linear chains ofamino acids joined in a peptide bonds. It is thus understandable that in Landsteiner’s monumental monograph on The Specificity of Serological Reactions he cautiously attributed the specificity of antisera to a “…the disproportional action ofa number of similar agents on a variety of related substrata” (1). By agents, he meant antibodies, of course, and by substrata he meant antigens or haptens. Today, having the benefit of over 60 years of further intensive study in many laboratories we can define specificity simply and more clearly as the ability “…to bind one unique chemical structure more strongly than a number of similar alternatives” (2).