Michael Heidelberger and the demystification of antibodies

Having defined the protein nature of antibodies under the tutelage of Oswald Avery, Michael Heidelberger was the first to apply mathematics to the reaction of antibodies and their antigens (the “precipitin reaction”). Heidelberger's calculations launched decades of research that helped reveal the specificity, function, and origin of antibodies.

Quantitative precipitin reaction and enzyme-linked immunosorbent assay of mannans of Candida albicans NIH A-207 and NIH B-792 strains compared.

We assessed the difference between results by enzyme-linked immunosorbent assay (EIA) in plastic support wells and the quantitative precipitin reaction (QPR) in glass test tubes for antigenic mannans and antibodies of two representative Candida albicans strains, NIH A-207 and NIH B-792. We investigated each of four mannan subfractions, with different phosphate contents, for their reactivities to the homologous polyclonal rabbit antiserum. Each series of mannan subfractions showed a reactivity proportional to their phosphate content in EIA, in a similar manner as observed in QPR. Moreover, in EIA, the cross-reactivities between the bulk mannans of the two C. albicans strains and the polyclonal antiserum of a Saccharomyces cerevisiae wild-type strain containing specific antibodies to the non-reducing terminal alpha-1,3-linked D-mannopyranose unit resembled those of the same antigen-antibody reactions in QPR. However, the mannan of C. albicans NIH A-207 strains, a weak antigen in the cross-QPR system, reacted fairly strongly in EIA in its high concentration range, indicating that EIA can be used to detect such an epitope in these mannans in concentrations undetectable by QPR. We conclude that EIA is a useful technique for immunochemical assay of yeast mannans and their antibodies on a smaller scale than with QPR.