Elimination of self-tolerogen turns nonresponder mice into responders.

Two sets of genes control the immune response of H-2d mice to the synthetic antigen poly(Glu50Tyr50) (GT). One set involves class II major histocompatibility complex (Mhc) loci encoding an Ad product that serves as a recognition context to GT-reactive helper T cells (Th). The other one is a background gene, the product of which, in association with the same Mhc-restricting element, mimics the GT/Ad complex. Mice expressing the GT-mimicking background-encoded structure (Imgt), which is preferentially displayed on B lymphoblasts, do not respond to GT as a consequence of self-tolerance. On the other hand, elimination of cells bearing Imgt renders these mice responsive to GT, demonstrating that tolerance to self can impoverish the immune system. Imgt is probably not identical to GT, but resembles it in the way it forms complexes with Ad molecules of Mhc.