Paul H. Maurer

IN VITRO RESPONSES UNDER I REGION CONTROL

Current work on two stages of the humoral antibody response which are under Ir gene control is summarized. The T cell macrophage interaction is under the control of two different genes, mapping in the I-A subregion, which influence either the macrophage factor or its receptor site on T cells. The repertoire of recognition of Ia by these T cells shows ‘self-preference’ - responses were not induced by allogeneic macrophages. The response of B cells to (T,G)-A--L helper factors of high potency (i.e. can be diluted to 10 --4 ) were studied. These factors bind to anti-Ia, anti-Ig and antigen-coated columns. The full activity can be eluted under acid conditions from each of the immunoadsorbants, indicating that all three activities exist as a complex. This factor acts on B cells indirectly, via macrophages.

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.

IMMUNE RESPONSES OF MICE AGAINST MODIFIED RANDOM POLYMERS OF AMINO ACIDS, AND IMPLICATIONS IN GENE CONTROL

Abstract The introduction of limited amounts (about 5–10%) of amino acids into the nonimmunogenic random copolymer poly(Glu60Lys40), GL, produces conjugates that exhibit variable immunogenicity in all strains of mice. The modified GL derivatives are T cell independent antigens, elicit IgM responses, and are B cell mitogens. Similar modification of the polymers GA, GAL10, GLT5 and GLOS, the responses against which are under Ir gene(s) control, did not alter the strain distribution patterns (SDP) so as to convert nonresponder mice to responders. The above observations and the known SDP against a number of GL terpolymers are discussed with speculations to help explain: 1) the immunogenicity of the amino acid modified GL polymer; 2) the nonimmunogenicity of GL in mice; 3) the unique SDP against the GL terpolymers; 4) the divergent immune response data obtained with the same polymer in different laboratories.

Multigenic I Region Control of the Immune Responses of Mice to the GLØ and GLT Random Terpolymers

Studies in several species have shown that immune responsiveness to random polymers of amino acids is controlled by histocompatibility-1inked immune response genes (Ir genes) (McDevitt and Landy 1972). In mice, we have characterized Ir genes controlling responsiveness to the terpolymers, poly(Glu58Lys38Phe4 (GLO) (Merryman et al. 1972), poly (Glu57Lys38Tyr5) (GLT5) and poly (G1u55Lys34Tyr15) (GLT15) (Merryman and Maurer 1975). The gene(s) controlling the responses to GLO and GLT5 were mapped to the IC subregion of H-2 (or to the right of the IB subregion) (Merryman and Maurer 1975). At the time we were aware of some “nonconcordant” negative responses obtained with some recombinant strains which had a responder allele in IC, i.e. ICd. Here we present: a) the positive responses to GLT and GLO obtained by F1 (C57BL/6 × A/J) derived from two non-responder parental strains which help explain the “nonconcordant” data, and b) data with H-2 recombinant mice that indicate the presence of another gene to the left of IC, making the GLO response under the control of at least two genes which map in two different subregions of the I region.

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.