I-A Mutation resulted in a selective loss of an antigen-specificIr gene function

Abstract

The immune responses to several antigens were compared in the I‐A mutant mouse strain B6.C‐H‐2^bm12 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‐A^b region. B6.C‐H‐2^bm12 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 la molecule, functions as a histocompatibility, la, and MLR antigen, as well as a necessary component for Ir gene function. Furthermore, the data reported here demonstrate that la molecules have multiple functional “Ir determinants,” one of which has been altered in the B6.C‐H‐2^bm12 mutant. The B6.C‐H‐2^bm12 mice, therefore, represent a powerful analytical tool for the understanding of the cellular and molecular basis for Ir gene control of the immune response.