Ia.W39 expression correlates with a specific Ir function.

The xid- defective mouse (N X B6)F1 male and the I-Ab mutant of the B6 mouse bm12 have mutations on different chromosomes, and therefore in separate genes. However, both variant strains have a trait in common; namely, they are unresponsive to the A chain loop determinant(s) of beef insulin to which mice of the H-2b haplotype respond. We show here that in both mutant strains, this unresponsiveness is concurrent with the absence of the Ia.W39 specificity from the M phi and B cell surface. The concordance is specific for Ia specificity W39 and no other Ia determinant, suggesting that Ia.W39 is identical with the Ir epitope necessary for generating an immune response to a particular amino acid sequence of beef insulin. In the xid-defective mouse, the molecule carrying this antigen is synthesized but not expressed on the plasma membrane, presumably because a mature M phi and B cell subset is missing. By comparison, the bm12 mouse has mature B lymphocytes, but is unable to synthesize Ia.W39. Thus, bm12 has a structural mutation in the gene coding for Ia.W39, whereas xid is a mutant regulatory or maturation gene controlling the membrane expression of Ia.W39.