Genetic Control of Immune Responses to Synthetic Polypeptides in Mice: Cellular Analysis of the Phenotypic Correction of the Ir-3 Gene Defect by Polyadenylic-Polyuridylic Acid

Abstract

Abstract Antibody responses to the multichain synthetic polypeptide poly (L Tyr, L Glu)-poly L Pro-poly L Lys, (T, G)-Pro--L, and to the Pro-L portion of the related polymer poly (L Phe, L Glu)-poly L Pro--poly L Lys, (Phe, G)-Pro--L, are controlled by the dominant, autosomal, non-H-2-linked, Ir-3 gene. SJL/J and DBA/1 mice are the respective high and low responder strains to Pro-L. Injection of low responder DBA/1 mice with 300 µg poly(A)·poly(U) 24 hr after immunization with either of these immunogens resulted in an enhancement of DBA/1 anti-Pro--L titers which were indistinguishable from those of untreated or poly(A)·poly(U)-treated SJL/J mice. In contrast, no effect of poly(A)·poly(U) on enhancing the antibody responses to poly (L Phe, L Glu)-poly DL Ala--poly L Lys, (Phe, G)-A-L, or to the (Phe, G) immunopotent region of (Phe, G)-Pro-L (immune responses controlled by the H-2-linked Ir-1 gene) was obtained. The anti-Pro--L response was also enhanced in another low responder strain, DBA/2. Thus, the effects of poly(A)·poly(U) described here are selective for phenotypic “correction” of antibody responses controlled by the Ir-3 gene only, and confirm that the modes of action of the Ir-1 and Ir-3 genes are distinct. Enhancement of the DBA/1 anti-Pro--L response using (Phe, G)-Pro-L, which contains two immunopotent regions, occurred at the expense of the anti-(Phe, G) response. Limiting dilution patterns of low responder spleen and marrow cells were quantitatively and qualitatively affected by administering poly(A)·poly(U) to the syngeneic hosts 24 hr after immunization with (T, G)-Pro--L. No effect of the polynucleotide was detected for dilutions of SJL/J high responder spleen cells, nor for those of DBA/1 low responder thymocytes. The lack of effect of poly(A)·poly(U) on thymocytes was verified in a two-step experimental design by exposing the thymocytes to antigen and the polynucleotide in the absence of marrow cells, followed by transferring the thymus-derived and marrow cells to irradiated test recipients. These results, as well as those (published elsewhere) for the Pro--L specific response, are compatible with the hypothesis that the immunologic effect of the Ir-3 gene is expressed at the level of cell-to-cell interaction, and that poly(A)·poly(U) immunologically “corrects” expression of this gene by making the interaction of the complementary cell types more effective.