Paul Pinchuck

Antibody Formation: Initiation in "Nonresponder" Mice by Macrophage Synthetic Polypeptide RNA

The RNA extracted from normal peritoneal macrophages exposed to a linear, random synthetic polypeptide, Glu60Ala30Tyr10, initiated an immune response in C57B1/6J mice, although this strain responds very poorly to the antigen itself. From 10 to 150 micrograms of RNA obtained from mouse, rat, or rabbit macrophages was injected intraperitoneally into recipient mice, and specific antibody was detectable by passive hemagglutination 3 to 4 weeks later. Treatment of the RNA with ribonuclease destroyed its ability to initiate a specific immune response. The RNA contained by weight 0.02 percent of the (specific) antigen. The RNA obtained from cells incubated with a second polypeptide, Glu36Lys24Ala40, initiated a response specific for this polymer. This RNA even when incubated in vitro with Glu60Ala30Tyr10 failed to initiate antibody formation specific for Glu60Ala30Tyr10.

ANTIGENICITY OF POLYPEPTIDES (POLY ALPHA AMINO ACIDS). XIV. STUDIES ON IMMUNOLOGICAL TOLERANCE WITH STRUCTURALLY RELATED SYNTHETIC POLYMERS.

Summary It. has been shown that neonatal injections of the polymers G60A40 and G42L28A30 can establish acquired immunological tolerance against these homologous polymers. Neonatal injections of polyglutamic acid are more effective than G42L28A30 in establishing cross tolerance against G60A40. Neither polyglutamic acid nor G60L40 when injected neonatally. were effective in reducing an adult, response against G42L28A30. However, G60A40 did reduce the response against a first course of immunization with G42L28A30. This tolerance was broken by a second immunization with polymer in complete adjuvants.

Antigenicity of polypeptides (poly-α-amino acids)—XVIII. Quantitative relationships among polymers containing glutamic acid, lysine and/or alannine rabbit antisera

Abstract Homologous and cross reactions of synthetic polymers of α-L-amino acids having different proportions of glutamic acid (G), lysin (L) and or alanin (A), were studied to learn the nature of the antigenic determinants in the polymers. With the Glu-Lys-Ala series, as the amount of alanine the glu-lys random polumers was increased, the specificity of the resulting antibody was altered. More of the antibody reactivity was directed against glu-lys and glu-ala determinants and less against glu-lys determinants. In the GA polumers, more polyglutamic acid specificity was present in G 60 A 40 and less in G 40 A 60 . In the latter polumer, more alanyl specificity was evident. An analogy is presented that the GLA and GA polymers having about equimolar amounts of these amino acids resemble globular and fibrous-like proteins respectively as juedged by their immunochemical behavior and in passive cutaneous anaphylaxis reactions.

Importance of Immunogenicity of the Carrier in Inducing a Response against Carrier-Synthetic Polymer Aggregates

During the past decade various types of synthetic polymers of amino acids have been used to study many areas of immunology and immuno-chemistry. Perhaps the most valuable information obtained has been relative to the requirements for immunogenicity, that is, the ability of a macromolecule to cause an animal to produce antibodies having specificity for some part of the polypeptide.

Effect of Prior Exposure to Synthetic Polymers of α-D-Amino Acids on the Subsequent Response to the Enantiomorphic Polymers of α-L-Amino Acids

Summary Previous injections of rabbits with poorly immunogenic polymers of α-D-am-ino acids in complete adjuvant reduced the subsequent response against the α-L-ami-no acid polymers when in complete adjuvant. No depressing effect was obtained when solutions of the α-D-amino acid polymer were injected intraperitoneally or intravenously. The above findings have been ascribed to the antigenic competition effect of the mycobacterial antigens for pluripotential antibody forming cells.