TRANSCRIPTION AND WEAK EXPRESSION OF HLA-DRB6 - A GENE WITH ANOMALIESIN EXON-1 AND OTHER REGIONS

HLA-DRB6 is one of the human major histocompatibility complex (MHC) ge nes present in DR1, DR2, and DR10 haplotypes (approximately 26% of ind ividuals). It shows several anomalies in human and non-human primates, including exon 2 stop codons (non-randomly grouped between codons 74 and 94) and a promoter region, and an exon 1 coming from an inserted r etrovirus. II has been shown that not only chimpanzee but also human M hc-DRB6 lack the usual 3' untranslated (UT) polyadenylation signal, an d in the present work it was found that the human DRB6 gene coming fro m an HLA-DR2 haplotype is effectively transcribed after transection in mouse L cells, and that HLA-DRB6 molecules may be expressed on the ce ll surface. DRB6 transcription level is remarkably lower in human than in chimpanzee. Moreover, their exons 1 (both taken from the 3'LTR reg ion of a mammary tumor retrovirus) are also different; this shows that these viral insertions may be an important mechanism for different ev olutionary changes in orthologous genes of different species. The path ways by which DRB6 molecules may be expressed on the membrane are uncl ear but other examples of truncated protein expression have also been described, even within the human major histocompatibility complex (i. e., in HLA-G). Finally, the presence of mature HLA-DRB6 mRNA molecules supports the notion that splicing may take place even in the absence of a canonical 3'UT polyadenylation signal.