LOW HLA-C EXPRESSION AT CELL-SURFACES CORRELATES WITH INCREASED TURNOVER OF HEAVY-CHAIN MESSENGER-RNA

In comparison with HLA-A and -B, the protein products of the HLA-C loc us are poorly characterized, in part because of their low level of exp ression at the cell surface. Here, we examine how protein-protein inte ractions during assembly and regulation of the mRNA level affect cell surface expression of HLA-C. We find that intrinsic properties of the HLA-C heavy chain proteins do not correlate with low cell surface expr ession: HLA-C heavy chains associate and dissociate with beta(2)-micro globulin (beta(2)m) at rates comparable to those found for HLA-A and - B, and increased competition for beta(2)m does not alter the surface e xpression of HLA-C. From studies of chimeric genes spliced from the HL A-B7 and -Cw3 genes, we find that chimeric proteins containing the B7 peptide-binding groove can have low cell surface expression, suggestin g that inefficiency in binding peptides is not the cause of low cell s urface expression for HLA-C. The surface levels of HLA-A, -B, or -C in cells transfected with cDNA can be similar, implicating noncoding reg ions of HLA-C heavy chain genes in the regulation of surface expressio n. We find that HLA-C mRNA is expressed at lower levels than HLA-B mRN A and that this difference results from faster degradation of the HLA- C message. Experiments examining chimeric B7/Cw3 and B7/Cw6 genes sugg est that a region determining low expression of HLA-C is to be found b etween the 3' end of exon 3 and a site in the 3' untranslated region, similar to 600 bases downstream of the translation stop codon.