Low HLA-C expression at cell surfaces correlates with increased turnover of heavy chain mRNA

Jane A. McCutcheon, Jenny Gumperz, Kelly D. Smith, Charles T. Lutz, Peter Parham

Research output: Contribution to journalArticlepeer-review

Abstract

In comparison with HLA-A and -B, the protein products of the HLA-C locus are poorly characterized, in part because of their low level of expression at the cell surface. Here, we examine how protein-protein interactions 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 expression: HLA-C heavy chains associate and dissociate with dissociate with ß2-microglobulin (ß2m) at rates comparable to those found for HLA-A and -B, and increased competition for ß2m does not alter the surface expression of HLA-C. From studies of chimeric genes spliced from the HLA-B7 and -Cw3 genes, we find that chimeric proteins containing the B7 peptide-binding groove can have low cell surface expression, suggesting that inefficiency in binding peptides is not the cause of low cell surface expression for HLA-C. The surface levels of HLA-A, -B, or -C in cells transfected with cDNA can be similar, implicating noncoding regions of HLA-C heavy chain genes in the regulation of surface expression. We find that HLA-C mRNA is expressed at lower levels than HLA-B mRNA and that this difference results from faster degradation of the HLA-C message. Experiments examining chimeric B7/Cw3 and B7/Cw6 genes suggest that a region determining low expression of HLA-C is to be found between the 3' end of exon 3 and a site in the 3' untranslated region, '~600 bases downstream of the translation stop codon.

Original languageEnglish (US)
Pages (from-to)2085-2095
Number of pages11
JournalJournal of Experimental Medicine
Volume181
Issue number6
DOIs
StatePublished - Jun 1 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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