Genetic control of the immune response: ability of antigens of defined amino acid sequence to be recognized by the Ir-1 gene system.

Mice were injected with a series of (T,G)-A--L[poly (L Tyr, L Glu)-poly DL Ala)--poly (L Lys)]-like compounds with side chains of homogeneous sequences: T-A--L, GT-A--L, GGT-A--L, and TG-A--L. T-A--L was not immunogenic. However, T-A--L was able to bind antibodies to (T, G)-A--L 509, and this binding could not be blocked by A--L. When complexed with bovine serum albumin, T-A--L, was immunogenic in both responder and nonresponder strains of mice. GT-A--L and GGT-A--L were both immunogenic and elicited the characteristic responder-nonresponder difference induced by (T,G)-A--L. TG-A--L was also immunogenic, but there was considerable overlap in the response of responder and nonresponder strains. On the average, responder mouse serum had a slightly higher antigen-binding capacity than nonresponder mouse serum. In contrast to antibodies against GGT-A--L, antibodies against TG-A--L bound heterologous antigens poorly. These data, along with the results of other investigators, are consistent with the hypothesis that there are multiple Ir- 1 genes which recognize different sequences. The specificity of the Ir- 1 genes is extraordinary. The polypeptides TG-A--L, TGTG-A--L and GTTG-A--L do not appear to be recognized by these genes.