I-A mutation resulted in a selective loss of an antigen-specific Ir gene function.

The immune responses to several antigens were compared in the I-A mutant mouse strain B6.C-H-2bm12 and the wild-type strain C57BL/6. With a lymph node cell proliferation assay, the response to two of these antigens, beef insulin and (TG)A-L, was demonstrated to be controlled by a gene in the I-Ab region. B6.C-H-2bm12 mice failed to respond to beef insulin, while their responses to (TG)A-L, DNP-OVA and PPD were comparable with those of the wild-type strain C57BL/6. Taken together with previous studies, these data suggest that the product of a single pleiotropic I-A gene, an Ia molecule, functions as a histocompatibility, Ia, and MLR antigen, as well as a necessary component for Ir gene function. Furthermore, the data reported here demonstrate that Ia molecules have multiple functional "Ir determinants," one of which has been altered in the B6.C-H-2bm12 mutant. The B6.C-H-2bm12 mice, therefore, represent a powerful analytical tool for the understanding of the cellular and molecular basis for Ir gene control of the immune response.