Antigenicity of Polypeptides (Poly Alpha Amino Acids)

Abstract

The antigenicity of synthetic polymers of a-amino acids has been studied in various species for different reasons. The original impetus to these investigations was the search for highly polymerized protein-like materials that could possibly be used as plasma volume expanders. Interest in these materials has increased since their anfigenicity offers a means of determining the minimum structural requirements for anfigenicity in protein-like materials. By the application of quantitative immunochemical studies with small polypeptides it may be possible to determine the size and structure of the antigenic unit and the nature of combining sites in the antibody.Previous reports have dealt with the antigenicity in humans of synthetic poly-a-glutamic acid (1) and random copolymers of glutamic acid and lysine (2). The present report will deal with the study in humans of additional copolymers consisting of 3 and 4 amino acids. The anfigenicity of the 4 polymers used in this study has been established previously in rabbits (3) and guinea pigs (4). Materials and MethodsThe copolymers studied for antigenicity in humans are listed in Table I. The methods used in preparing the materials and the techniques employed in determining the average molecular weights are presented in references 5-10. After withdrawal of 50 ml of blood the human volunteers were skln-tested with 0.1 ml of polymer solutions of 10 mg/ml and 1 mg/ml and 0.1 ml of the 0.15 ~ saline buffer. The individuals then received 5 intramuscular injections of the appropriate polymer solutions given over a period of 10 days. With antigens GLA5 and GLT a total of 125 mg was injected into 6 and 5 individuals respectively. With antigens GLA40 and GLAT, 6 individuals in each group received a total of 12.5 mg and other groups of 6 received 125 mg. The bleedings and skin testings were repeated about 12 and 21 days after the last injection.

Antigenicity of Polypeptides (Poly Alpha Amino Acids)

“…Previously it was reported that 1/3 Hartley strain guinea pig sera (anti GLAT) cross reacted with the G60L40 polymer (11) and that of 5 human sera (anti GLAT) 3 gave cross reactions with G60L40 (13). As the data in Table VII shows, even sera which have a similar cross reaction with one polymer may differ as regards a second heterologous reaction.…”

“…In previous reports on the immunogenicity in man (13) and guinea pigs (11) of a random straight chain polymer containing the aL amino acids glutamic acid36 lysine24 alanine35 and tyro sines** (GLAT) reference has been made to the immunogenicity in rabbits and mice. However data accumulated during the years dealing with extensive findings in rabbits and mice have not been reported.…”

Antigenicity of Polypeptides (Poly Alpha Amino Acids)

“…for immunizing rabbits and guinea pigs have been referred to in the previous publications (1)(2)(3)(4)(5)(6)(7)(8).…”

Studies on Artificial Antigens

“…In contrast, random copolymers containing comparable amounts of 3 or 4 L-amino acids, such as glutamic acid, lysine, and alanine (GLA), 1 or glutamic acid, alanine, and tyrosine (GAT), or GLAT, have been found to be antigenic in rabbits. (2, 3), guinea pigs (4), and man (5), in nearly every subject tested. Random copolymers of 2 L-amino acids GA, GL, or LA, induce also an immune response in guinea pigs (4,6) but only in some animals and not in others.…”