Pauling wrote a chapter for the 1945 revised edition of Landsteiner’s book, The Specificity of Serological Reactions titled “Molecular Structure and Intermolecular Forces.” In his chapter, Pauling stressed the importance of intermolecular interactions, which he defined as van der Waals interactions, hydrogen bonds and other weak bonds. Additionally, he stated that specificity in immunology was most likely due to intermolecular interactions, rather than the breaking and forming of strong bonds. Pauling had developed his ideas about chemical bonds in his various publications on The Nature of the Chemical Bond and in his chemistry textbooks.

He also noted that the specificity of an antibody to a particular antigen depended upon complementariness in structure. Pauling stated that the surface structure of compounds determines how strongly two compounds bind to one another in the antigen-antibody reaction. In other words, if the two compounds are highly complementary, then they can clamp on tightly to one another.

Five years before undertaking this chapter for the 1945 edition of Landsteiner’s book, Pauling had written a theoretical article, in which he presented a theory on the formation of antibodies. Following up on notions about the behavior of globulin, a polypeptide chain that folds itself into a stable structure and becomes the antibody, Pauling proposed six steps to explain how antibodies form onto an antigen. Step one: an uncoiled globulin surrounds the antigen. Two: both ends of the globulin begin folding around the antigen and the complementary parts of the globulin and antigen attach. The active surface region of the antigen dictates the folding of globulin; thus, numerous configurations are possible. Three: the middle section of the globulin frees itself. Four: one end of the globulin detaches from the antigen. Five: the globulin coils into its stable structure; it is now an antibody. The sixth and final step: the antibody detaches from the antigen. Pauling also erroneously suggested that all antibodies have the same amino acids sequences in their polypeptide chains, but that the polypeptide chains fold differently. Pauling gathered a substantial amount of immunochemical information with help from others, especially Dan H. Campbell, associate professor of immunochemistry and research fellow David Pressman.