Studies on Synthetic Polypeptide Antigens

Studies of systematically varied series of synthetic polypeptides lead to several generalizations about the chemical factors involved in antigenicity. Polymers containing aromatic amino acids generally elicit more antibody than those not containing aromatic amino acids. This is not an exclusive property, however, since the incorporation of alanine can enhance immunogenicity in some cases. Tyrosine and phenylalanine are equally effective in enhancing antibody formation, but there is no correlation between the amount of antibody elicited and the amount of the aromatic amino acid in the polypeptide. The charge of the antigen plays essentially a restrictive role: completely charged and highly charged polypeptides are very poor immunogens. The immunogenicity of d -amino acid polymers and the stereospecificity of the antibody response have been confirmed, and the reason for the difficulty in eliciting antibody formation has been established. Immunization with the relatively large doses of antigen used with l polymers (2 to 20 mg) does not generally elicit antibody formation with d antigens, but low doses (0.3 to 0.6 mg) of antigen administered over a long period of time induce antibody formation to a wide variety of d -polypeptides. The d polymers do not display a significant booster effect, and eventually the antibody response is abolished by continued injection of the antigen. Using this same low dosage schedule, polylysine and polyglutamic acid of both optical configurations also elicit antibody. Thus, the generalization can be made that small doses of poor immunogens stimulate antibody formation and larger doses induce immunological paralysis. The experiments described in this study suggest that the method needed to induce antibody formation is determined by quite general properties of the antigen (e.g. optical configuration, excessively high charge) and that the quantitative control of antibody production depends upon both the general properties and the detailed composition of the antigen (e.g. types of amino acids).