Insights into immune-response gene function using an Ia mutant mouse strain.

The class II genes of the major histocompatibility complex (MHC) encode the immune response-associated or Ia antigens. These highly polymorphic glycoprotein heterodimers have been shown to play a pivotal role in diverse immunological functions. Although the precise molecular and cellular interactions have yet to be elucidated, structural determinations on Ia molecules are known to control the immune response to foreign antigens. Several recent advances into our understanding of how Ia molecules function were made possible by the discovery of the B6,C-H-2bm12 (bm12) mouse strain. The bm12 strain carries a mutation that occurred spontaneously in one of its genes encoding an Ia polypeptide chain. Information from studies using bm12 include (1) insights into the evolution of class II genes and its functional significance; (2) the definition of multiple functional sites on Ia and their relative importance; and (3) the demonstration that Ia conformation is important in determining its functional capacity. These findings using the bm12 mutant are reviewed in the context of other recent studies of Ia recognition.