MECHANISM OF ANTIBODY FORMATION 79 



are dissimilar, 1.28X10"'^, and out of 20 naturally known amino 

 acids 2.4X10^^ protein isomers could be formed. It must be under- 

 stood that such a polypeptide, as well as any protein, exists, or can 

 exist in numerous tautomeric forms, each of which will have properties 

 different from the other. 



In proteins the amino acids are bound together by peptide bonds 

 through a-amino and a-carboxyl groups and the rest of the amino acid 

 is essentially free. The non-peptide forming parts of the amino acids 

 constitute side groupings in a protein molecule. The amino acids are 

 listed below (Table I); according to their side groupings they con- 

 tribute to the structure of the protein molecule. As will be seen, they 

 are acidic, basic, polar and hydrophobic. These characteristics are 

 related to free carboxyl, amino, amide, guanidine, phenolic, aliphatic 

 hydroxyl, indole imino, imidazole NH, methyl sulfide, disulfide 

 groups, and phenyl and aliphatic hydrophobic hydrocarbon radicals. 



Studies with enzymes, hormones, viruses (simple), and antigens deal 

 with specific chemical reactions with certain of these side groupings in 

 relation to their reversible and irreversible inactivation. Despite ex- 

 tensive investigation the nature of enzymatic and antigenic specificity 

 of the proteins remains the challenging unsolved problem. It is true, 

 for example, that the oxidation of SH groups, or the reduction of 

 -S-S- groups destroys the activity of certain proteins, but this fact alone 

 does not explain the specific activity of various enzymes to which the 

 same reactive SH or -S-S- groups are attached. There is no doubt that 

 these specificities are governed by the whole protein molecule or parts 

 thereof larger than the SH or similar groups. 



The integrity of every constituent part of the protein molecule 

 functioning as virus, enzyme, hormone or antigen is essential for full 

 biological activity. A scission in the molecule usually causes complete 

 loss of activity. In this respect, the ability of an antigen to initiate 

 the production of a specific antibody is comparable to those of enzymes 

 and hormones. Splitting of a protein of minimal molecular unit size 

 causes loss of the ability to stimulate antibody formation. This property 

 of antigen being catalytic in character differs from its ability to 

 combine with homologous antibody. In the latter case the reaction is 

 stoichiometrical, is independent of molecular size and, therefore, of 

 the integrity of the whole antigenic molecule. As is well known, the 

 split products, as haptens, enter into stoichiometrical combination with 



