Class II antigen processing defects in two H2(d) mouse cell lines are caused by point mutations in the H2-DMa gene

The molecular nature of the defect in two mouse antigen processing-defectiv e cell lines was examined. Both mutants were derived from the A20 (BALB/c, H2(d)) B cell line, and both were found to have defects in the H2-DMa gene. Mutant 3A5 exhibits severely reduced amounts of H2-DMa message, and no det ectable DM alpha protein. cDNA sequence revealed a C-->T transition at nucl eotide 118, introducing a premature stop codon in exon 2 of the H2-DMa gene . In contrast, mutant 2A2 exhibits reduced but detectable levels of H2-DMa message and DM alpha protein only after treatment with IL-4, which induces the expression of both the H2-DMa and the H2-DMb genes in B cells. In this mutant the cDNA sequence revealed a missense mutation in exon 3 resulting i n the conversion of a conserved proline residue in the Ig-like domain to se rine. Stable transfection with full-length H2-DMa cDNA reconstitutes the an tigen processing capacity of both mutants, as demonstrated by the ability t o present native antigen to T cell clones, and by restored class II SDS sta bility.