Studies on the chemical basis of the antigenicity of proteins. 6. Antigenic specificity of some synthetic polypeptides containing tyrosine

Abstract

Rabbit antisera to several synthetic linear and multichain copolypeptides, containing tyrosine as well as glut am ic acid, alanine and/or lysine, were allowed to react with various chemically related and unrelated linear and multichain polypeptides, proteins and polypeptidyl proteins. The extent of reaction was followed by cross-precipitation or by inhibition of the homologous reaction. The synthetic polypeptide antigens investigated contain determinants of well-defined and rather narrow immune specificity. Substances which are not immunogenic, because the area important for immunogenicity is not accessible to the biosynthetic site, may nevertheless cross-react with antibodies formed against substances closely related chemically. Apparently the capacity of a molecule to react with the combining site of an antibody is not parallel with its ability to elicit the formation of antibodies. The antigenic specificity is governed by the area of the molecule most exposed to the surroundings. Antibodies to linear polypeptide antigens gave much better precipitation with linear than with multichain polymers. The efficiency of inhibition of some systems with specificity directed to peptides of tyrosine and glutamic acid by means of copolymers of tyrosine and glutamic acid was strongly dependent on the molar ratio of two amino acids in the copolymer. Some copolymers caused complete inhibition of the homologous reaction of the system p(Tyr, Glu)[long dash]p-Lys-anti-p(Tyr,Glu)-pLys. The molar ratios of 2 such inhibitors to the immunogen at 50% of the total inhibition were 70 and 94.