Use of Synthetic Polymers of Amino Acids to Study the Basis of Antigenicity (Part 1 of 2)

Abstract

Review with 106 references. Studies with synthetic polymers of amino acids have begun to contribute to our knowledge about the chemical and structural bases for antigenicity of macromolecules. The immunogenicity of polymeric materials appear to be related primarily to the genetic background of the host and possible to their ability to be hydrolyzed by enzymes. This is demonstrated by immune reactions in random bred versus inbred animals and the non antigenicity of polymers consisting of D amino acids. Antibody production has been shown to be directed predominantly against the areas most accessible to enzyme action. Another important factor contributing to antigenicity is the diversity of structure of the antigen. Linear polymers such as cellulose and homopolymers of the amino acids are not antigenic whereas bacterial polysaccharides and copolymers of amino acids are antigenic. The appearance of antigenicity in non antigenic homopolymers after coupling to proteins or small haptenes such as 2,4 dinitroaniline also attest to this idea. That copolymers containing about equimolar amounts of the two amino acids are better antigens than copolymers containing predominantly one amino acid may be related to the formation of more diverse random structures in the former. The net charge of the macromolecule does not contribute to antigenicity and the role of molecular weight is minor. The nature of antigenic determinants, sizes of the antigenic unit and antibody sites can be studied with the synthetic polypeptides. Because of the random and heterogeneous nature of the polymers, these studies are beset by many difficulties. Cross reactions between various polymers or proteins give only a gross insight into the problem, i.e. antisera to polypeptides containing both glutamic acid and lysine (with or without a third amino acid) reacted well with polypeptides containing both glutamic acid and lysine and a third amino acid. No cross reactions were noted (in vitro or in vivo) of proteins with the many antisera studied. Similarly, the terpoly-mers discussed in this review have not reacted with several rabbit antisera (anti human or bovine serum albumin and gamma globulin). This would indicate the more complex nature of the antigenic areas of native proteins compared to synthetic polyamino acids and the feasibility of undertaking inhibition studies of the anti-polypeptide sera with related peptides. Also, estimation of the size of an antigenic (or antibody) site by extrapolation from limited inhibition data with amino acids or dipeptides does not seem justified. The use of higher oligopeptides appears more promising. This idea is supported by the absence of inhibition of anti G6OA40 or anti G42L28A30 sera by di-and tripeptides of glutamic acid (or alanine) and its effective inhibition by the penta and hexa glutamic acid peptides and by the reaction of poly G with these antisera. (Poly G also reacted with antisera against G57L38A5 and G58L38T4 but poly lysine did not.) The next phase of investigation, which may be most fruitful, is the preparation and study of the antigenicity of polymers of known amino acid sequence, such as (glu glu ala)n or (glu ala glu)n etc.