mRNA abundance, rather than differences in subunit assembly, determine differential expression of HLA-DR beta 1 and...

The class II major histocompatibility molecules HLA-DR are formed by the association of a single DR alpha chain with two nonallelic DR beta chains. In DR3 cells one DR beta chain is severalfold more abundant than the other. We have studied the mechanism that controls the differential expression of these DR beta genes. We determined the amino-terminal sequences of the two expressed DR beta chains. Comparison of these sequences with the nucleotide sequences of the DR3B1 and DRB3a genes indicates that the abundant chain is the B1 gene product. Supporting this conclusion, an informative mutant, 9.4.3, was found to have lost the abundant beta chain and beta 1 mRNA. This mutant expresses normal cell surface levels of the DR beta 3 chain and exhibits no significant dosage compensation of its beta 3 chain. The unchanged level of DR beta 3 dimer on the cell surface suggests that free DR alpha chains are not the limiting factor in the surface expression of the beta 3 chain and, further, that the differential regulation of the surface expression of the two DR beta chains occurs at a step prior to DR assembly. Quantitation of DR beta mRNAs by locus-specific oligonucleotide probes showed that beta 1 mRNA is 4.5-fold more abundant than beta 3 mRNA, strongly indicating that the greater surface expression of DR beta 1 is a direct consequence of greater beta 1 mRNA abundance.